Proteins (also known as polypeptides) are organic compounds An organic compound is any member of a large class of chemical compounds whose molecules contain carbon. For historical reasons discussed below, a few types of compounds such as carbonates, simple oxides of carbon and cyanides, as well as the allotropes of carbon, are considered inorganic. The distinction between "organic" and " made of amino acids Amino acids are molecules containing an amine group, a carboxylic acid group and a side chain that varies between different amino acids. These molecules contain the key elements of carbon, hydrogen, oxygen, and nitrogen. These molecules are particularly important in biochemistry, where this term refers to alpha-amino acids with the general formula arranged in a linear chain and folded into a globular form. The amino acids in a polymer A polymer is a large molecule composed of repeating structural units typically connected by covalent chemical bonds. While polymer in popular usage suggests plastic, the term actually refers to a large class of natural and synthetic materials with a wide variety of properties are joined together by the peptide bonds This article is for the peptide link found within biological molecules, such as proteins. A similar article for synthetic molecules is being created. Be aware that, although the atoms involved are the same, the terms amide link and peptide link cannot be used interchangedly between the carboxyl Carboxylic acids are organic acids characterized by the presence of at least one carboxyl group. The general formula of a carboxylic acid is R-COOH, where R is some monovalent functional group and amino Amines are organic compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group. Important amines include amino acids, biogenic amines, trimethylamine, and aniline; see Category:Amines for groups of adjacent amino acid residues In chemistry, residue refers to the material remaining after a distillation or an evaporation, or to a portion of a larger molecule, such as a methyl group. It may also refer to the undesired byproducts of a reaction. The sequence of amino acids in a protein is defined by the sequence The primary structure of a biological molecule is the exact specification of its atomic composition and the chemical bonds connecting those atoms. As nucleic acids, e.g. DNA and RNA, are unbranched polymers, this is equivalent to specifying exact sequence of nucleotides that comprise the whole molecule. This sequence is written as a succession of of a gene A gene is a unit of heredity in a living organism. It is normally a stretch of DNA that codes for a type of protein or for an RNA chain that has a function in the organism. All living things depend on genes, as they specify all proteins and functional RNA chains. Genes hold the information to build and maintain an organism's cells and pass genetic, which is encoded in the genetic code The genetic code is the set of rules by which information encoded in genetic material is translated into proteins (amino acid sequences) by living cells. The code defines a mapping between tri-nucleotide sequences, called codons, and amino acids. With some exceptions, a triplet codon in a nucleic acid sequence specifies a single amino acid.[1] In general, the genetic code specifies 20 standard amino acids; however, in certain organisms the genetic code can include selenocysteine Selenocysteine is an amino acid that is present in several enzymes—and in certain archaea The Archaea (/ɑrˈkiːə/ ar-KEE-ə) are a group of single-celled microorganisms. A single individual or species from this domain is called an archaeon (sometimes spelled "archeon"). They have no cell nucleus or any other organelles within their cells. In the past they were viewed as an unusual group of bacteria and named archaebacteria—pyrrolysine Pyrrolysine is a naturally occurring, genetically coded amino acid used by some methanogenic archaea and one known bacterium in enzymes that are part of their methane-producing metabolism. It is similar to lysine, but with an added pyrroline ring linked to the end of the lysine side chain. Produced by a specific tRNA and aminoacyl tRNA synthetase,. Shortly after or even during synthesis, the residues in a protein are often chemically modified by post-translational modification Posttranslational modification is the chemical modification of a protein after its translation. It is one of the later steps in protein biosynthesis for many proteins, which alters the physical and chemical properties, folding, stability, activity, and ultimately, the function of the proteins. Proteins can also work together to achieve a particular function, and they often associate to form stable complexes A multiprotein complex is a group of two or more associated polypeptide chains. If the different polypeptide chains contain different protein domain, the resulting multiprotein complex can have multiple catalytic functions. This is distinct from a multienzyme polypeptide, in which multiple catalyic domains are found in a single polypeptide chain.[2]

Like other biological macromolecules A macromolecule is a very large molecule most often created by some form of polymerization. In the context of biochemistry, the term may be applied to the four conventional biopolymers , as well as non-polymeric molecules with large molecular mass such as macrocycles. The constituent molecules from which macromolecules are assembled are called such as polysaccharides Polysaccharides are polymeric carbohydrate structures, formed of repeating units joined together by glycosidic bonds. These structures are often linear, but may contain various degrees of branching. Polysaccharides are often quite heterogeneous, containing slight modifications of the repeating unit. Depending on the structure, these macromolecules and nucleic acids A nucleic acid is a macromolecule composed of chains of monomeric nucleotides. In biochemistry these molecules carry genetic information or form structures within cells. The most common nucleic acids are deoxyribonucleic acid and ribonucleic acid (RNA). Nucleic acids are universal in living things, as they are found in all cells and viruses, proteins are essential parts of organisms and participate in virtually every process within cells The cell is the functional basic unit of life. It was discovered by Robert Hooke and is the functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. Some organisms, such as most bacteria, are unicellular . Other organisms, such as humans,. Many proteins are enzymes Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process are called substrates, and the enzyme converts them into different molecules, called the products. Almost all processes in a biological cell need enzymes to occur at significant rates. Since enzymes are selective for their that catalyze Catalysis is the change in rate of a chemical reaction due to the participation of a substance called a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. A catalyst may participate in multiple chemical transformations. Catalysts that speed the reaction are called positive biochemical reactions and are vital to metabolism Metabolism is the set of chemical reactions that happen in living organisms to maintain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories. Catabolism breaks down organic matter, for example to harvest energy in cellular. Proteins also have structural or mechanical functions, such as actin Actin is a globular, roughly 42-kDa protein found in all eukaryotic cells where it may be present at concentrations of over 100 μM. It is also one of the most highly-conserved proteins, differing by no more than 20% in species as diverse as algae and humans. Actin is the monomeric subunit of two types of filaments in cells: microfilaments, one of and myosin Myosins are a large family of motor proteins found in eukaryotic tissues. They are responsible for actin-based motility in muscle and the proteins in the cytoskeleton The cytoskeleton is a cellular "scaffolding" or "skeleton" contained within the cytoplasm and is made out of protein. The cytoskeleton is present in both plant and animal cells. The cytoskeleton was once thought to be unique to eukaryotes, but recent research has identified the prokaryotic cytoskeleton. It is a dynamic, which form a system of scaffolding Scaffolding is a temporary structure used to support people and material in the construction or repair of buildings and other large structures. It is usually a modular system of metal pipes or tubes, although it can be made out of other materials. Bamboo is still used in some Asian countries like People's Republic of China that maintains cell shape. Other proteins are important in cell signaling Cell signaling is part of a complex system of communication that governs basic cellular activities and coordinates cell actions. The ability of cells to perceive and correctly respond to their microenvironment is the basis of development, tissue repair, and immunity as well as normal tissue homeostasis. Errors in cellular information processing, immune responses Antibodies are gamma globulin proteins that are found in blood or other bodily fluids of vertebrates, and are used by the immune system to identify and neutralize foreign objects, such as bacteria and viruses. They are typically made of basic structural units—each with two large heavy chains and two small light chains—to form, for example,, cell adhesion Cellular adhesion is the binding of a cell to a surface, extracellular matrix or another cell using cell adhesion molecules such as selectins, integrins, and cadherins, and the cell cycle The cell cycle, or cell-division cycle, is the series of events that takes place in a cell leading to its division and duplication . In cells without a nucleus (prokaryotic), the cell cycle occurs via a process termed binary fission. In cells with a nucleus (eukaryotes), the cell cycle can be divided in two brief periods: interphase—during which. Proteins are also necessary in animals' diets, since animals cannot synthesize all the amino acids they need and must obtain essential amino acids An essential amino acid or indispensable amino acid is an amino acid that cannot be synthesized de novo by the organism , and therefore must be supplied in the diet from food. Through the process of digestion In mammals, food enters the mouth, being chewed by teeth, with chemical processing beginning with chemicals in the saliva from the salivary glands. Then it travels down the esophagus into the stomach, where hydrochloric acid kills most contaminating microorganisms and begins mechanical break down of some food , and chemical alteration of some. The, animals break down ingested protein into free amino acids that are then used in metabolism.

Proteins were first described by the Dutch Catholicism, Protestantism , Nontheism chemist Gerhardus Johannes Mulder Gerardus Johannes Mulder earned a medical degree from Utrecht University. Mulder was a Dutch organic and analytical chemist who became a professor of chemistry at Rotterdam and later at Utrecht. While at the Utrecht University, Mulder described the chemical composition of protein. He claimed that albuminous substances are made up of a common and named by the Swedish chemist Jöns Jakob Berzelius Friherre Jöns Jacob Berzelius was a Swedish chemist. He worked out the modern technique of chemical formula notation, and is together with John Dalton, Antoine Lavoisier, and Robert Boyle considered a father of modern chemistry. He began his career as a physician but his researches in physical chemistry were of lasting significance in the in 1838. Early nutritional scientists such as the German Carl von Voit believed that protein was the most important nutrient for maintaining the structure of the body, because it was generally believed that "flesh makes flesh."[3] The central role of proteins as enzymes in living organisms was however not fully appreciated until 1926, when James B. Sumner James Batcheller Sumner was an American chemist. He shared the Nobel Prize in Chemistry in 1946 with John Howard Northrop and Wendell Meredith Stanley showed that the enzyme urease Urease is an enzyme that catalyzes the hydrolysis of urea into carbon dioxide and ammonia. The reaction occurs as follows: was in fact a protein.[4] The first protein to be sequenced was insulin Insulin is a hormone that is central to regulate energy and glucose metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle, by Frederick Sanger Frederick Sanger, OM, CH, CBE, FRS is an English biochemist and twice a Nobel laureate in chemistry. He is the fourth (and only living) person to have been awarded two Nobel Prizes, who won the Nobel Prize for this achievement in 1958. The first protein structures to be solved were hemoglobin Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of vertebrates, and the tissues of some invertebrates. Hemoglobin in the blood is what transports oxygen from the lungs or gills to the rest of the body (i.e. the tissues) where it releases the oxygen for cell use and myoglobin Myoglobin is an iron- and oxygen-binding protein found in the muscle tissue of vertebrates in general and in almost all mammals. It is related to hemoglobin, which is the iron- and oxygen-binding protein in blood, specifically in the red blood cells. The only time myoglobin is found in the bloodstream is when it is released following muscle injury, by Max Perutz Max Ferdinand Perutz, OM, CBE was an Austrian-born British molecular biologist, who was awarded the Nobel Prize for Chemistry in 1962, shared with John Kendrew for their studies of the structures of hemoglobin and globular proteins. At Cambridge he supervised the PhD work of Francis Crick and James Watson in the Cavendish Laboratory as they and Sir John Cowdery Kendrew Sir John Cowdery Kendrew, CBE, FRS was an English biochemist and crystallographer who shared the 1962 Nobel Prize in Chemistry with Max Perutz; their group in the Cavendish Laboratory investigated the structure of heme-containing proteins, respectively, in 1958.[5][6] The three-dimensional structures of both proteins were first determined by x-ray diffraction analysis; Perutz and Kendrew shared the 1962 Nobel Prize in Chemistry The Nobel Prize in Chemistry is awarded annually by the Royal Swedish Academy of Sciences to scientists in the various fields of chemistry. It is one of the five Nobel Prizes established by the will of Alfred Nobel in 1895, awarded for outstanding contributions in chemistry, physics, literature, peace, and physiology or medicine. This award is for these discoveries. Proteins may be purified Protein purification is a series of processes intended to isolate a single type of protein from a complex mixture. Protein purification is vital for the characterisation of the function, structure and interactions of the protein of interest. The starting material is usually a biological tissue or a microbial culture. The various steps in the from other cellular components using a variety of techniques such as ultracentrifugation Differential centrifugation is a common procedure in microbiology and cytology used to separate certain organelles from whole cells for further analysis of specific parts of cells. In the process, a tissue sample is first homogenised to break the cell membranes and mix up the cell contents. The homogenate is then subjected to repeated, precipitation Precipitation is the formation of a solid in a solution or inside another solid during a chemical reaction or by diffusion in a solid. When the reaction occurs in a liquid, the solid formed is called the precipitate, and the liquid remaining above the solid is called the supernate. Powders derived from precipitation have also historically been, electrophoresis Electrophoresis is the motion of dispersed particles relative to a fluid under the influence of a spatially uniform electric field. This electrokinetic phenomenon was observed for the first time in 1807 by Reuss, who noticed that the application of a constant electric field caused clay particles dispersed in water to migrate. It is ultimately, and chromatography Chromatography is the collective term for a set of laboratory techniques for the separation of mixtures. It involves passing a mixture dissolved in a "mobile phase" through a stationary phase, which separates the analyte to be measured from other molecules in the mixture based on differential partitioning between the mobile and; the advent of genetic engineering Genetic engineering, recombinant DNA technology, genetic modification/manipulation , and gene splicing are terms that apply to the direct manipulation of an organism's genes. Genetic engineering is different from traditional breeding, where the organism's genes are manipulated indirectly. Genetic engineering uses the techniques of molecular has made possible a number of methods to facilitate purification. Methods commonly used to study protein structure and function include immunohistochemistry, site-directed mutagenesis, and mass spectrometry.

Contents

Biochemistry

Main articles: Biochemistry, Amino acid, and peptide bond A representation of the 3D structure of myoglobin showing coloured alpha helices. This protein was the first to have its structure solved by X-ray crystallography. Resonance structures of the peptide bond that links individual amino acids to form a protein polymer.

Most proteins are linear polymers built from series of up to 20 different L-α-amino acids. All amino acids possess common structural features, including an α-carbon to which an amino group, a carboxyl group, and a variable side chain are bonded. Only proline differs from this basic structure as it contains an unusual ring to the N-end amine group, which forces the CO–NH amide moiety into a fixed conformation.[7] The side chains of the standard amino acids, detailed in the list of standard amino acids, have a great variety of chemical structures and properties; it is the combined effect of all of the amino acid side chains in a protein that ultimately determines its three-dimensional structure and its chemical reactivity.[8]

Chemical structure of the peptide bond (left) and a peptide bond between leucine and threonine (right).

The amino acids in a polypeptide chain are linked by peptide bonds. Once linked in the protein chain, an individual amino acid is called a residue, and the linked series of carbon, nitrogen, and oxygen atoms are known as the main chain or protein backbone.[9] The peptide bond has two resonance forms that contribute some double-bond character and inhibit rotation around its axis, so that the alpha carbons are roughly coplanar. The other two dihedral angles in the peptide bond determine the local shape assumed by the protein backbone.[10] The end of the protein with a free carboxyl group is known as the C-terminus or carboxy terminus, whereas the end with a free amino group is known as the N-terminus or amino terminus.

The words protein, polypeptide, and peptide are a little ambiguous and can overlap in meaning. Protein is generally used to refer to the complete biological molecule in a stable conformation, whereas peptide is generally reserved for a short amino acid oligomers often lacking a stable three-dimensional structure. However, the boundary between the two is not well defined and usually lies near 20–30 residues.[11] Polypeptide can refer to any single linear chain of amino acids, usually regardless of length, but often implies an absence of a defined conformation.

Synthesis

Main article: Protein biosynthesis The DNA sequence of a gene encodes the amino acid sequence of a protein.

Proteins are assembled from amino acids using information encoded in genes. Each protein has its own unique amino acid sequence that is specified by the nucleotide sequence of the gene encoding this protein. The genetic code is a set of three-nucleotide sets called codons and each three-nucleotide combination designates an amino acid, for example AUG (adenine-uracil-guanine) is the code for methionine. Because DNA contains four nucleotides, the total number of possible codons is 64; hence, there is some redundancy in the genetic code, with some amino acids specified by more than one codon.[12] Genes encoded in DNA are first transcribed into pre-messenger RNA (mRNA) by proteins such as RNA polymerase. Most organisms then process the pre-mRNA (also known as a primary transcript) using various forms of post-transcriptional modification to form the mature mRNA, which is then used as a template for protein synthesis by the ribosome. In prokaryotes the mRNA may either be used as soon as it is produced, or be bound by a ribosome after having moved away from the nucleoid. In contrast, eukaryotes make mRNA in the cell nucleus and then translocate it across the nuclear membrane into the cytoplasm, where protein synthesis then takes place. The rate of protein synthesis is higher in prokaryotes than eukaryotes and can reach up to 20 amino acids per second.[13]

The process of synthesizing a protein from an mRNA template is known as translation. The mRNA is loaded onto the ribosome and is read three nucleotides at a time by matching each codon to its base pairing anticodon located on a transfer RNA molecule, which carries the amino acid corresponding to the codon it recognizes. The enzyme aminoacyl tRNA synthetase "charges" the tRNA molecules with the correct amino acids. The growing polypeptide is often termed the nascent chain. Proteins are always biosynthesized from N-terminus to C-terminus.[12]

The size of a synthesized protein can be measured by the number of amino acids it contains and by its total molecular mass, which is normally reported in units of daltons (synonymous with atomic mass units), or the derivative unit kilodalton (kDa). Yeast proteins are on average 466 amino acids long and 53 kDa in mass.[11] The largest known proteins are the titins, a component of the muscle sarcomere, with a molecular mass of almost 3,000 kDa and a total length of almost 27,000 amino acids.[14]

Chemical synthesis

Short proteins can also be synthesized chemically by a family of methods known as peptide synthesis, which rely on organic synthesis techniques such as chemical ligation to produce peptides in high yield.[15] Chemical synthesis allows for the introduction of non-natural amino acids into polypeptide chains, such as attachment of fluorescent probes to amino acid side chains.[16] These methods are useful in laboratory biochemistry and cell biology, though generally not for commercial applications. Chemical synthesis is inefficient for polypeptides longer than about 300 amino acids, and the synthesized proteins may not readily assume their native tertiary structure. Most chemical synthesis methods proceed from C-terminus to N-terminus, opposite the biological reaction.[17]

Structure of proteins

Main article: Protein structure Three possible representations of the three-dimensional structure of the protein triose phosphate isomerase. Left: all-atom representation colored by atom type. Middle: Simplified representation illustrating the backbone conformation, colored by secondary structure. Right: Solvent-accessible surface representation colored by residue type (acidic residues red, basic residues blue, polar residues green, nonpolar residues white).

Most proteins fold into unique 3-dimensional structures. The shape into which a protein naturally folds is known as its native conformation.[18] Although many proteins can fold unassisted, simply through the chemical properties of their amino acids, others require the aid of molecular chaperones to fold into their native states.[19] Biochemists often refer to four distinct aspects of a protein's structure:[20]

Proteins are not entirely rigid molecules. In addition to these levels of structure, proteins may shift between several related structures while they perform their functions. In the context of these functional rearrangements, these tertiary or quaternary structures are usually referred to as "conformations", and transitions between them are called conformational changes. Such changes are often induced by the binding of a substrate molecule to an enzyme's active site, or the physical region of the protein that participates in chemical catalysis. In solution proteins also undergo variation in structure through thermal vibration and the collision with other molecules.[21]

Molecular surface of several proteins showing their comparative sizes. From left to right are: immunoglobulin G (IgG, an antibody), hemoglobin, insulin (a hormone), adenylate kinase (an enzyme), and glutamine synthetase (an enzyme).

Proteins can be informally divided into three main classes, which correlate with typical tertiary structures: globular proteins, fibrous proteins, and membrane proteins. Almost all globular proteins are soluble and many are enzymes. Fibrous proteins are often structural, such as collagen, the major component of connective tissue, or keratin, the protein component of hair and nails. Membrane proteins often serve as receptors or provide channels for polar or charged molecules to pass through the cell membrane.[22]

A special case of intramolecular hydrogen bonds within proteins, poorly shielded from water attack and hence promoting their own dehydration, are called dehydrons.[23]

Structure determination

Discovering the tertiary structure of a protein, or the quaternary structure of its complexes, can provide important clues about how the protein performs its function. Common experimental methods of structure determination include X-ray crystallography and NMR spectroscopy, both of which can produce information at atomic resolution. However, NMR experiments are able to provide information from which a subset of distances between pairs of atoms can be estimated, and the final possible conformations for a protein are determined by solving a distance geometry problem. Dual polarisation interferometry is a quantitative analytical method for measuring the overall protein conformation and conformational changes due to interactions or other stimulus. Circular dichroism is another laboratory technique for determining internal beta sheet/ helical composition of proteins. Cryoelectron microscopy is used to produce lower-resolution structural information about very large protein complexes, including assembled viruses;[24] a variant known as electron crystallography can also produce high-resolution information in some cases , especially for two-dimensional crystals of membrane proteins.[25] Solved structures are usually deposited in the Protein Data Bank (PDB), a freely available resource from which structural data about thousands of proteins can be obtained in the form of Cartesian coordinates for each atom in the protein.[26]

Many more gene sequences are known than protein structures. Further, the set of solved structures is biased toward proteins that can be easily subjected to the conditions required in X-ray crystallography, one of the major structure determination methods. In particular, globular proteins are comparatively easy to crystallize in preparation for X-ray crystallography. Membrane proteins, by contrast, are difficult to crystallize and are underrepresented in the PDB.[27] Structural genomics initiatives have attempted to remedy these deficiencies by systematically solving representative structures of major fold classes. Protein structure prediction methods attempt to provide a means of generating a plausible structure for proteins whose structures have not been experimentally determined.

Cellular functions

Proteins are the chief actors within the cell, said to be carrying out the duties specified by the information encoded in genes.[11] With the exception of certain types of RNA, most other biological molecules are relatively inert elements upon which proteins act. Proteins make up half the dry weight of an Escherichia coli cell, whereas other macromolecules such as DNA and RNA make up only 3% and 20%, respectively.[28] The set of proteins expressed in a particular cell or cell type is known as its proteome.

The enzyme hexokinase is shown as a simple ball-and-stick molecular model. To scale in the top right-hand corner are two of its substrates, ATP and glucose.

The chief characteristic of proteins that also allows their diverse set of functions is their ability to bind other molecules specifically and tightly. The region of the protein responsible for binding another molecule is known as the binding site and is often a depression or "pocket" on the molecular surface. This binding ability is mediated by the tertiary structure of the protein, which defines the binding site pocket, and by the chemical properties of the surrounding amino acids' side chains. Protein binding can be extraordinarily tight and specific; for example, the ribonuclease inhibitor protein binds to human angiogenin with a sub-femtomolar dissociation constant (<10−15 M) but does not bind at all to its amphibian homolog onconase (>1 M). Extremely minor chemical changes such as the addition of a single methyl group to a binding partner can sometimes suffice to nearly eliminate binding; for example, the aminoacyl tRNA synthetase specific to the amino acid valine discriminates against the very similar side chain of the amino acid isoleucine.[29]

Proteins can bind to other proteins as well as to small-molecule substrates. When proteins bind specifically to other copies of the same molecule, they can oligomerize to form fibrils; this process occurs often in structural proteins that consist of globular monomers that self-associate to form rigid fibers. Protein–protein interactions also regulate enzymatic activity, control progression through the cell cycle, and allow the assembly of large protein complexes that carry out many closely related reactions with a common biological function. Proteins can also bind to, or even be integrated into, cell membranes. The ability of binding partners to induce conformational changes in proteins allows the construction of enormously complex signaling networks.[30] Importantly, as interactions between proteins are reversible, and depend heavily on the availability of different groups of partner proteins to form aggregates that are capable to carry out discrete sets of function, study of the interactions between specific proteins is a key to understand important aspects of cellular function, and ultimately the properties that distinguish particular cell types[31][32].

Enzymes

Main article: Enzyme

The best-known role of proteins in the cell is as enzymes, which catalyze chemical reactions. Enzymes are usually highly specific and accelerate only one or a few chemical reactions. Enzymes carry out most of the reactions involved in metabolism, as well as manipulating DNA in processes such as DNA replication, DNA repair, and transcription. Some enzymes act on other proteins to add or remove chemical groups in a process known as post-translational modification. About 4,000 reactions are known to be catalyzed by enzymes.[33] The rate acceleration conferred by enzymatic catalysis is often enormous — as much as 1017-fold increase in rate over the uncatalyzed reaction in the case of orotate decarboxylase (78 million years without the enzyme, 18 milliseconds with the enzyme).[34]

The molecules bound and acted upon by enzymes are called substrates. Although enzymes can consist of hundreds of amino acids, it is usually only a small fraction of the residues that come in contact with the substrate, and an even smaller fraction — 3 to 4 residues on average — that are directly involved in catalysis.[35] The region of the enzyme that binds the substrate and contains the catalytic residues is known as the active site.

Cell signaling and ligand binding

Ribbon diagram of a mouse antibody against cholera that binds a carbohydrate antigen

Many proteins are involved in the process of cell signaling and signal transduction. Some proteins, such as insulin, are extracellular proteins that transmit a signal from the cell in which they were synthesized to other cells in distant tissues. Others are membrane proteins that act as receptors whose main function is to bind a signaling molecule and induce a biochemical response in the cell. Many receptors have a binding site exposed on the cell surface and an effector domain within the cell, which may have enzymatic activity or may undergo a conformational change detected by other proteins within the cell.[36]

Antibodies are protein components of adaptive immune system whose main function is to bind antigens, or foreign substances in the body, and target them for destruction. Antibodies can be secreted into the extracellular environment or anchored in the membranes of specialized B cells known as plasma cells. Whereas enzymes are limited in their binding affinity for their substrates by the necessity of conducting their reaction, antibodies have no such constraints. An antibody's binding affinity to its target is extraordinarily high.[37]

Many ligand transport proteins bind particular small biomolecules and transport them to other locations in the body of a multicellular organism. These proteins must have a high binding affinity when their ligand is present in high concentrations, but must also release the ligand when it is present at low concentrations in the target tissues. The canonical example of a ligand-binding protein is haemoglobin, which transports oxygen from the lungs to other organs and tissues in all vertebrates and has close homologs in every biological kingdom.[38] Lectins are sugar-binding proteins which are highly specific for their sugar moieties. Lectins typically play a role in biological recognition phenomena involving cells and proteins.[39] Receptors and hormones are highly specific binding proteins.

Transmembrane proteins can also serve as ligand transport proteins that alter the permeability of the cell membrane to small molecules and ions. The membrane alone has a hydrophobic core through which polar or charged molecules cannot diffuse. Membrane proteins contain internal channels that allow such molecules to enter and exit the cell. Many ion channel proteins are specialized to select for only a particular ion; for example, potassium and sodium channels often discriminate for only one of the two ions.[40]

Structural proteins

Structural proteins confer stiffness and rigidity to otherwise-fluid biological components. Most structural proteins are fibrous proteins; for example, actin and tubulin are globular and soluble as monomers, but polymerize to form long, stiff fibers that comprise the cytoskeleton, which allows the cell to maintain its shape and size. Collagen and elastin are critical components of connective tissue such as cartilage, and keratin is found in hard or filamentous structures such as hair, nails, feathers, hooves, and some animal shells.[41]

Other proteins that serve structural functions are motor proteins such as myosin, kinesin, and dynein, which are capable of generating mechanical forces. These proteins are crucial for cellular motility of single celled organisms and the sperm of many multicellular organisms which reproduce sexually. They also generate the forces exerted by contracting muscles.[42]

Methods of study

Main article: Protein methods

As some of the most commonly studied biological molecules, the activities and structures of proteins are examined both in vitro and in vivo. In vitro studies of purified proteins in controlled environments are useful for learning how a protein carries out its function: for example, enzyme kinetics studies explore the chemical mechanism of an enzyme's catalytic activity and its relative affinity for various possible substrate molecules. By contrast, in vivo experiments on proteins' activities within cells or even within whole organisms can provide complementary information about where a protein functions and how it is regulated.

Protein purification

Main article: Protein purification

In order to perform in vitro analysis, a protein must be purified away from other cellular components. This process usually begins with cell lysis, in which a cell's membrane is disrupted and its internal contents released into a solution known as a crude lysate. The resulting mixture can be purified using ultracentrifugation, which fractionates the various cellular components into fractions containing soluble proteins; membrane lipids and proteins; cellular organelles, and nucleic acids. Precipitation by a method known as salting out can concentrate the proteins from this lysate. Various types of chromatography are then used to isolate the protein or proteins of interest based on properties such as molecular weight, net charge and binding affinity.[43] The level of purification can be monitored using various types of gel electrophoresis if the desired protein's molecular weight and isoelectric point are known, by spectroscopy if the protein has distinguishable spectroscopic features, or by enzyme assays if the protein has enzymatic activity. Additionally, proteins can be isolated according their charge using electrofocusing.[44]

For natural proteins, a series of purification steps may be necessary to obtain protein sufficiently pure for laboratory applications. To simplify this process, genetic engineering is often used to add chemical features to proteins that make them easier to purify without affecting their structure or activity. Here, a "tag" consisting of a specific amino acid sequence, often a series of histidine residues (a "His-tag"), is attached to one terminus of the protein. As a result, when the lysate is passed over a chromatography column containing nickel, the histidine residues ligate the nickel and attach to the column while the untagged components of the lysate pass unimpeded. A number of different tags have been developed to help researchers purify specific proteins from complex mixtures.[45]

Cellular localization

Proteins in different cellular compartments and structures tagged with green fluorescent protein) (here, white).

The study of proteins in vivo is often concerned with the synthesis and localization of the protein within the cell. Although many intracellular proteins are synthesized in the cytoplasm and membrane-bound or secreted proteins in the endoplasmic reticulum, the specifics of how proteins are targeted to specific organelles or cellular structures is often unclear. A useful technique for assessing cellular localization uses genetic engineering to express in a cell a fusion protein or chimera consisting of the natural protein of interest linked to a "reporter" such as green fluorescent protein (GFP).[46] The fused protein's position within the cell can be cleanly and efficiently visualized using microscopy,[47] as shown in the figure opposite.

Other methods for elucidating the cellular location of proteins requires the use of known compartmental markers for regions such as the ER, the Golgi, lysosomes/vacuoles, mitochondria, chloroplasts, plasma membrane, etc. With the use of fluorescently tagged versions of these markers or of antibodies to known markers, it becomes much simpler to identify the localization of a protein of interest. For example, indirect immunofluorescence will allow for fluorescence colocalization and demonstration of location. Fluorescent dyes are used to label cellular compartments for a similar purpose.[48]

Other possibilities exist, as well. For example, immunohistochemistry usually utilizes an antibody to one or more proteins of interest that are conjugated to enzymes yielding either luminescent or chromogenic signals that can be compared between samples, allowing for localization information. Another applicable technique is cofractionation in sucrose (or other material) gradients using isopycnic centrifugation.[49] While this technique does not prove colocalization of a compartment of known density and the protein of interest, it does increase the likelihood, and is more amenable to large-scale studies.

Finally, the gold-standard method of cellular localization is immunoelectron microscopy. This technique also uses an antibody to the protein of interest, along with classical electron microscopy techniques. The sample is prepared for normal electron microscopic examination, and then treated with an antibody to the protein of interest that is conjugated to an extremely electro-dense material, usually gold. This allows for the localization of both ultrastructural details as well as the protein of interest.[50]

Through another genetic engineering application known as site-directed mutagenesis, researchers can alter the protein sequence and hence its structure, cellular localization, and susceptibility to regulation. This technique even allows the incorporation of unnatural amino acids into proteins, using modified tRNAs,[51] and may allow the rational design of new proteins with novel properties.[52]

Proteomics and bioinformatics

Main articles: Proteomics and Bioinformatics

The total complement of proteins present at a time in a cell or cell type is known as its proteome, and the study of such large-scale data sets defines the field of proteomics, named by analogy to the related field of genomics. Key experimental techniques in proteomics include 2D electrophoresis,[53] which allows the separation of a large number of proteins, mass spectrometry,[54] which allows rapid high-throughput identification of proteins and sequencing of peptides (most often after in-gel digestion), protein microarrays,[55] which allow the detection of the relative levels of a large number of proteins present in a cell, and two-hybrid screening, which allows the systematic exploration of protein–protein interactions.[56] The total complement of biologically possible such interactions is known as the interactome.[57] A systematic attempt to determine the structures of proteins representing every possible fold is known as structural genomics.[58]

The large amount of genomic and proteomic data available for a variety of organisms, including the human genome, allows researchers to efficiently identify homologous proteins in distantly related organisms by sequence alignment. Sequence profiling tools can perform more specific sequence manipulations such as restriction enzyme maps, open reading frame analyses for nucleotide sequences, and secondary structure prediction. From this data phylogenetic trees can be constructed and evolutionary hypotheses developed using special software like ClustalW regarding the ancestry of modern organisms and the genes they express. The field of bioinformatics seeks to assemble, annotate, and analyze genomic and proteomic data, applying computational techniques to biological problems such as gene finding and cladistics.

Structure prediction and simulation

Main articles: protein structure prediction and List of protein structure prediction software

Complementary to the field of structural genomics, protein structure prediction seeks to develop efficient ways to provide plausible models for proteins whose structures have not yet been determined experimentally [59]. The most successful type of structure prediction, known as homology modeling, relies on the existence of a "template" structure with sequence similarity to the protein being modeled; structural genomics' goal is to provide sufficient representation in solved structures to model most of those that remain.[60] Although producing accurate models remains a challenge when only distantly related template structures are available, it has been suggested that sequence alignment is the bottleneck in this process, as quite accurate models can be produced if a "perfect" sequence alignment is known.[61] Many structure prediction methods have served to inform the emerging field of protein engineering, in which novel protein folds have already been designed.[62] A more complex computational problem is the prediction of intermolecular interactions, such as in molecular docking and protein–protein interaction prediction.[63]

The processes of protein folding and binding can be simulated using such technique as molecular mechanics, in particular, molecular dynamics and Monte Carlo, which increasingly take advantage of parallel and distributed computing (Folding@Home project[64]; molecular modeling on GPU). The folding of small alpha-helical protein domains such as the villin headpiece[65] and the HIV accessory protein[66] have been successfully simulated in silico, and hybrid methods that combine standard molecular dynamics with quantum mechanics calculations have allowed exploration of the electronic states of rhodopsins.[67]

Nutrition

Further information: Protein (nutrient)

Most microorganisms and plants can biosynthesize all 20 standard amino acids, while animals (including humans) must obtain some of the amino acids from the diet.[28] The amino acids that an organism cannot synthesize on its own are referred to as essential amino acids. Key enzymes that synthesize certain amino acids are not present in animals — such as aspartokinase, which catalyzes the first step in the synthesis of lysine, methionine, and threonine from aspartate. If amino acids are present in the environment, microorganisms can conserve energy by taking up the amino acids from their surroundings and downregulating their biosynthetic pathways.

In animals, amino acids are obtained through the consumption of foods containing protein. Ingested proteins are then broken down into amino acids through digestion, which typically involves denaturation of the protein through exposure to acid and hydrolysis by enzymes called proteases. Some ingested amino acids are used for protein biosynthesis, while others are converted to glucose through gluconeogenesis, or fed into the citric acid cycle. This use of protein as a fuel is particularly important under starvation conditions as it allows the body's own proteins to be used to support life, particularly those found in muscle.[68] Amino acids are also an important dietary source of nitrogen.[citation needed]

History and etymology

Further information: History of molecular biology

Proteins were recognized as a distinct class of biological molecules in the eighteenth century by Antoine Fourcroy and others, distinguished by the molecules' ability to coagulate or flocculate under treatments with heat or acid. Noted examples at the time included albumin from egg whites, blood serum albumin, fibrin, and wheat gluten. Dutch chemist Gerhardus Johannes Mulder carried out elemental analysis of common proteins and found that nearly all proteins had the same empirical formula, C400H620N100O120P1S1.[69] He came to the erroneous conclusion that they might be composed of a single type of (very large) molecule. The term "protein" to describe these molecules was proposed in 1838 by Mulder's associate Jöns Jakob Berzelius; protein is derived from the Greek word πρωτεῖος (proteios), meaning "primary"[70], "in the lead", or "standing in front".[71] Mulder went on to identify the products of protein degradation such as the amino acid leucine for which he found a (nearly correct) molecular weight of 131 Da.[69]

The difficulty in purifying proteins in large quantities made them very difficult for early protein biochemists to study. Hence, early studies focused on proteins that could be purified in large quantities, e.g., those of blood, egg white, various toxins, and digestive/metabolic enzymes obtained from slaughterhouses. In the 1950s, the Armour Hot Dog Co. purified 1 kg of pure bovine pancreatic ribonuclease A and made it freely available to scientists; this gesture helped ribonuclease A become a major target for biochemical study for the following decades.[69]

Linus Pauling is credited with the successful prediction of regular protein secondary structures based on hydrogen bonding, an idea first put forth by William Astbury in 1933.[72] Later work by Walter Kauzmann on denaturation,[73][74] based partly on previous studies by Kaj Linderstrøm-Lang,[75] contributed an understanding of protein folding and structure mediated by hydrophobic interactions. In 1949 Fred Sanger correctly determined the amino acid sequence of insulin, thus conclusively demonstrating that proteins consisted of linear polymers of amino acids rather than branched chains, colloids, or cyclols.[76] The first atomic-resolution structures of proteins were solved by X-ray crystallography in the 1960s[77] and by NMR in the 1980s[77]. As of 2009, the Protein Data Bank has over 55,000 atomic-resolution structures of proteins.[78] In more recent times, cryo-electron microscopy of large macromolecular assemblies[79] and computational protein structure prediction of small protein domains[80] are two methods approaching atomic resolution.

See also

Wikimedia Commons has media related to: Proteins

Footnotes

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References

External links

Databases and projects

Tutorials and educational websites

Proteins
Processes Protein biosynthesis · Posttranslational modification · Protein folding · Protein targeting · Proteome · Protein methods
Structures Protein structure · Protein structural domains · Proteasome
Types List of types of proteins · List of proteins · Membrane protein · Globular protein (Globulin, Albumin) · Fibrous protein
biochemical : (, ) · (, , , , ) · (, , ) · /
Proteins: key methods of study
Experimental Protein purification · Green fluorescent protein · Western blot · Protein immunostaining · Protein sequencing · Gel electrophoresis/Protein electrophoresis · Protein immunoprecipitation · Peptide mass fingerprinting · Dual polarization interferometry · Chromatin immunoprecipitation
Bioinformatics Protein structure prediction · Protein–protein docking · Protein structural alignment · Protein ontology · Protein–protein interaction prediction
Assay Enzyme assay · Protein assay · Secretion assay
Display techniques Bacterial display · mRNA display · Phage display · Ribosome display · Yeast display
Super resolution microscopy Vertico SMI
Proteins: enzymes
Topics Active site · Allosteric regulation · Binding site · Catalytically perfect enzyme · Coenzyme · Cofactor · Cooperativity · EC number · Enzyme catalysis · Enzyme inhibitor · Enzyme kinetics · Lineweaver–Burk plot · Michaelis–Menten kinetics · List of enzymes
Types EC1 Oxidoreductases/list · EC2 Transferases/list · EC3 Hydrolases/list · EC4 Lyases/list · EC5 Isomerases/list · EC6 Ligases/list
Proteins of the cytoskeleton
Human
Microfilaments (ABPs)
Myofilament

Actins (A1, A2, B, C1, G1, G2)

Myosins (1A, 1B, 1C, MYH1, MYH2, MYH3, MYH4, MYH6, MYH7, MYH7B, MYH8, MYH9, MYH10, MYH11, MYH13, MYH14, MYH15, MYH16)

Tropomodulin (1, 2, 3, 4) · Troponin (T 1 2 3, C 1 2, I 1 2 3) · Tropomyosin (1, 2, 3, 4)

other related: Actinin (1, 2, 3, 4) · Arp2/3 complex · actin depolymerizing factors (Cofilin (1, 2) · Destrin) · Gelsolin · Profilin (1, 2) · Titin
Other Wiskott-Aldrich syndrome protein
IFs type 1 and 2 (Cytokeratin, type I, type II) · type 3 (Desmin, GFAP, Peripherin, Vimentin) · type 4 (Internexin, Nestin, Neurofilament, Synemin, Syncoilin) · type 5 (Lamin A, B)
Microtubules Dyneins · Kinesins · MAPs (Tau protein, Dynamin) · Tubulins · Stathmin · Tektin
Catenins Alpha catenin · Beta catenin · Plakoglobin (gamma catenin) · Delta catenin
Other APC · Dystrophin (Dystroglycan) · plakin (Desmoplakin, Plectin) · Spectrin (SPTA1, SPTAN1, SPTB, SPTBN1, SPTBN2, SPTBN4, SPTBN5) · Talin (TLN1) · Utrophin · Vinculin
Nonhuman Major sperm proteins · Prokaryotic cytoskeleton (Crescentin, FtsZ, MreB)
Protein, glycoconjugate: glycoproteins and glycopeptides
Mucoproteins
Mucin CD43 - CD164 - MUC1 - MUC2 - MUC3A - MUC3B - MUC4 - MUC5AC - MUC5B - MUC6 - MUC7 - MUC8 - MUC12 - MUC13 - MUC15 - MUC16 - MUC17 - MUC19 -MUC20
Other Haptoglobin - Intrinsic factor - Orosomucoid - Peptidoglycan - Phytohaemagglutinin - Ovomucin
Other Activin and inhibin · ADAM · Alpha 1-antichymotrypsin · Apolipoprotein H · CD70 · Asialoglycoprotein · Avidin · B-cell activating factor · 4-1BB ligand · Cholesterylester transfer protein · Clusterin · Colony-stimulating factor · Hemopexin · Lactoferrin · Membrane glycoproteins · Myelin protein zero · Osteonectin · Protein C · Protein S · Proteoglycan · Serum amyloid P component · Sialoglycoprotein (CD43, Glycophorin, Glycophorin C) · Thrombopoietin · Thyroglobulin · Thyroxine-binding proteins · Transcortin · Tumor necrosis factor-alpha · Uteroglobin · Vitronectin

: MET

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///, /, ///, ,

meds(A16, ),intm(////, ////, //)
biochemical : (, ) · (, , , , ) · (, , ) · /
Proteins: coagulation
Coagulation factors
Primary hemostasis

vWF

platelet membrane glycoproteins: Ib (A, B, IX) · IIb/IIIa (IIb, IIIa) · VI
Intrinsic pathway HMWK/Bradykinin · Prekallikrein/Kallikrein · XII "Hageman" XI · IX · VIII
Extrinsic pathway III "Tissue factor" · VII
Common pathway X · V · II "(Pro)thrombin" · I "Fibrin" XIII
Coagulation inhibitors Antithrombin (inhibits II, IX, X, XI, XII) · Protein C (inhibits V, VIII)/Protein S (cofactor for protein C) · Protein Z (inhibits X) · ZPI (inhibits X, XI) · TFPI (inhibits III)
Thrombolysis/fibrinolysis Plasmin · tPA/urokinase · PAI-1/2 · α2-AP · α2-macroglobulin · TAFI

: MYL

/ (, , )

//, /,

drug (//),

Proteins: complement system (C, L, A)
Activators/enzymes
Early

C: C1Q/C1R/C1S - C4 (C4a) - C2

L: MASP1/MASP2 - MBL
Middle

CLA: C3 (C3a, C3b/iC3b) - C5 (C5a)

A: Factor B - Factor D - Factor P/Properdin

CLA: C3-convertase - C5-convertase
Late CLA: MAC (C6, C7, C8, C9)
Inhibitors

CLA: C1-inhibitor - Decay accelerating factor - Factor I

CL: C4BP

A: Factor H
Complement receptors CR1 - CR2 - CR3 - CR4 - CD11b/CD11c/CD18 - Anaphylatoxin (C3a, C5a)
Proteins: carrier proteins
Fatty acid FABP1 · FABP2 · FABP3 · FABP4 · FABP5 · FABP6 · FABP7
Hormone Follistatin · Growth hormone binding protein · Insulin-like growth factor binding protein (IGFBP1, IGFBP2, IGFBP3, IGFBP4, IGFBP5, IGFBP6, IGFBP7) · Neurophysins (Neurophysin I, II) Sex hormone binding globulin/Androgen binding protein · Transcortin · Thyroxine-binding globulin · Transthyretin
Metal/element calcium (Calcium-binding protein, Calmodulin-binding proteins) · copper (Ceruloplasmin) · iron (Iron-binding proteins, Transferrin receptor)
Vitamin Retinol binding protein (4) · Transcobalamin
Other Acyl carrier protein · Adaptor protein · Cholesterylester transfer protein · F-box protein · GTP-binding protein · Latent TGF-beta binding protein · Light-harvesting complex · Major urinary proteins · Membrane transport protein · Odorant binding protein
Food chemistry

Additives · Carbohydrates · Coloring · Enzymes · Essential fatty acids · Flavors · Lipids · "Minerals" (Chemical elements) · Proteins · Vitamins · Water
Metabolism (Catabolism, Anabolism)
General Metabolic pathway · Metabolic network · Cellular respiration (Anaerobic/Aerobic)
Specific paths
Protein metabolism Protein synthesis · Amino acid synthesis · Catabolism Nucleotide metabolism: Purine metabolism · Nucleotide salvage · Pyrimidine metabolism
Carbohydrate metabolism
Anabolism Gluconeogenesis · Glycogenesis · Photosynthesis (Carbon fixation)
Carbohydrate catabolism Glycolysis · Glycogenolysis · Fermentation (ABE, Ethanol, Lactic acid) · Cellular respiration · Xylose metabolism
Other Pentose phosphate pathway · Glycosylation
Lipid metabolism (Lipolysis, Lipogenesis)
Fatty acid metabolism Fatty acid degradation (Beta oxidation) · Fatty acid synthesis
Other Eicosanoid metabolism · Sphingolipid metabolism · Steroid metabolism · Ketosis
Other Metal metabolism (Iron metabolism) · Ethanol metabolism

: MET

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Categories: Molecular biology | Nutrition | Proteins | Proteomics

 

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'Protein' News
The Pregnant Life: The Big Baby Weight - The Stir (blog)
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The Pregnant Life: The Big Baby Weight - The Stir (blog)
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The Stir (blog) Especially when they suddenly don't like your BP and there's protein in your urine. But I'm getting ahead of myself. The day started out fine -- Penelope ...
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Boring seemingly has the monopoly on backyards Holy Grail the day will come when the underdogs that is Team Exciting break through to win the most coverted trophy in Backyard Cricket Team Exciting Back Row L R Abbo Hardy Thommo Dyso

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Wed, 28 Jul 2010 23:22:44 GM

High . Protein. Low Carb Diet Plan - Is it Worthy It? High . Protein. Low Carb diet plans are very popular. Many people have used this kind of.

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'Protein' Answers
What are good sources of protein in average food?
Q. What are good sources of protein in average food? Also, is there a way I can drink protein shakes that will give me my protein (and possibly more, because more is better right?), without gaining a whole lot of weight? If they do have alot of calories, is there any way I can burn them off? I am 15 and I am very interested in body building, I am not doing it for looks or to become attractive, I want to do it to compete against myself. Thanks.
Asked by Ryan R - Fri Nov 30 21:11:22 2007 - - 6 Answers - 0 Comments

A. Some good sources of protein are: Protien shakes (like you said) cottage cheese fish (brioled or backed not fried) tuna fish egg whites If your loading on protiens you may need to take a good multi-vitamin suplament. Hope this helps you out!!!
Answered by mike_bellnj - Fri Nov 30 21:24:22 2007

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