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| ] showing coloured ]. This protein was the first to have its structure solved by ].]] | |||
| {{otheruses4|a class of biomolecules|alternate uses, such as ]|Protein (disambiguation)}} | |||
| '''Proteins''' are ]s made of ]s arranged in a linear chain and joined together by ]s between the ] and ] groups of adjacent amino acid ]. The sequence of amino acids in a protein is defined by the ] of a ], which is encoded in the ]. In general, the genetic code specifies 20 standard amino acids, however in certain organisms the genetic code can include ] - and in certain ] - ]. The residues in a protein are often observed to be chemically modified by ], which can happen either before the protein is used in the ], or as part of control mechanisms. Proteins can also work together to achieve a particular function, and they often associate to form stable ]es.<ref>{{cite book | |||
| | last = Maton | |||
| | first = Anthea | |||
| | authorlink = | |||
| | coauthors = Jean Hopkins, Charles William McLaughlin, Susan Johnson, Maryanna Quon Warner, David LaHart, Jill D. Wright | |||
| | title = Human Biology and Health | |||
| | publisher = Prentice Hall | |||
| | date = 1993 | |||
| | location = Englewood Cliffs, New Jersey, USA | |||
| | pages = | |||
| | url = | |||
| | doi = | |||
| | id = | |||
| | isbn = 0-13-981176-1 | |||
| | oclc = 32308337}}</ref> | |||
| Like other biological ] such as ]s and ]s, proteins are essential parts of organisms and participate in every process within ]s. Many proteins are ]s that ] biochemical reactions and are vital to ]. Proteins also have structural or mechanical functions, such as ] and ] in muscle and the proteins in the ], which form a system of ] that maintains cell shape. Other proteins are important in ], ]s, ], and the ]. Proteins are also necessary in animals' diets, since animals cannot synthesize all the amino acids they need and must obtain ]s from food. Through the process of ], animals break down ingested protein into free amino acids that are then used in metabolism. | |||
| The word ''protein'' comes from the ] word ''πρώτειος'' (''proteios'') "primary". Proteins were first described and named by the Swedish chemist ] in 1838. However, the central role of proteins in living organisms was not fully appreciated until 1926, when ] showed that the enzyme ] was a protein.<ref>{{cite journal |author=Sumner, JB |title=The Isolation and Crystallization of the Enzyme Urease. Preliminary Paper |url=http://www.jbc.org/cgi/reprint/69/2/435.pdf?ijkey=028d5e540dab50accbf86e01be08db51ef49008f |journal=J Biol Chem |volume=69 |issue= |pages=435–41 |year=1926}}</ref> The first protein to be sequenced was ], by ], who won the Nobel Prize for this achievement in 1958. The first protein structures to be solved included ] and ], by ] and ], respectively, in 1958.<ref>{{cite journal |author=Muirhead H, Perutz M |title=Structure of hemoglobin. A three-dimensional fourier synthesis of reduced human hemoglobin at 5.5 A resolution |journal=Nature |volume=199 |issue=4894 |pages=633–8 |year=1963 |pmid=14074546 |doi=10.1038/199633a0}}</ref><ref>{{cite journal |author=Kendrew J, Bodo G, Dintzis H, Parrish R, Wyckoff H, Phillips D |title=A three-dimensional model of the myoglobin molecule obtained by x-ray analysis |journal=Nature |volume=181 |issue=4610 |pages=662–6 |year=1958 |pmid=13517261 | doi = 10.1038/181662a0 <!--Retrieved from CrossRef by DOI bot-->}}</ref> The three-dimensional structures of both proteins were first determined by x-ray diffraction analysis; Perutz and Kendrew shared the 1962 ] for these discoveries. | |||
| ==Biochemistry== | |||
| {{main|Biochemistry|Amino acid|peptide bond}} | |||
| ] structures of the ] that links individual amino acids to form a protein ].]] | |||
| ] | |||
| Proteins are linear ]s built from 20 different <small>L</small>-α-]s. All amino acids possess common structural features, including an ] to which an ] group, a ] group, and a variable ] are ]. Only ] 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.<ref name=''Nelson''>Nelson, D. L. and Cox, M. M. (2005) Lehninger's Principles of Biochemistry, 4th Edition, W. H. Freeman and Company, New York.</ref> The side chains of the standard amino acids, detailed in the ], have different chemical properties that produce three-dimensional protein structure and different reactivities, are therefore critical to protein function.<ref>{{cite journal |author=Gutteridge A, Thornton JM |title=Understanding nature's catalytic toolkit |journal=Trends in biochemical sciences |volume=30 |issue=11 |pages=622–9 |year=2005 |month=November |pmid=16214343 |doi=10.1016/j.tibs.2005.09.006}}</ref> | |||
| The amino acids in a polypeptide chain are linked by ]s. 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.'' The peptide bond has two ] forms that contribute some ] character and inhibit rotation around its axis, so that the alpha carbons are roughly ]. The other two ]s in the peptide bond determine the local shape assumed by the protein backbone. | |||
| Due to the chemical structure of the individual amino acids, the protein chain has directionality. The end of the protein with a free carboxyl group is known as the ] or carboxy terminus, whereas the end with a free amino group is known as the ] or amino terminus. | |||
| The words ''protein'', ''],'' and '']'' are a little ambiguous and can overlap in meaning. ''Protein'' is generally used to refer to the complete biological molecule in a stable ], 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.<ref name="Lodish">Lodish H, Berk A, Matsudaira P, Kaiser CA, Krieger M, Scott MP, Zipurksy SL, Darnell J. (2004). ''Molecular Cell Biology'' 5th ed. WH Freeman and Company: New York, NY.</ref> ''Polypeptide'' can refer to any single linear chain of amino acids, usually regardless of length, but often implies an absence of a defined ]. | |||
| == Synthesis == | |||
| {{main article|Protein biosynthesis}} | |||
| ] sequence of a gene ] the ] sequence of a protein.]] | |||
| Proteins are assembled from amino acids using information encoded in ]s. Each protein has its own unique amino acid sequence that is specified by the ] sequence of the gene encoding this protein. The ] is a set of three-nucleotide sets called ]s and each three-nucleotide combination stands for an amino acid, for example AUG stands for ]. Because ] 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. Genes encoded in DNA are first ] into pre-] (mRNA) by proteins such as ]. Most organisms then process the pre-mRNA (also known as a ''primary transcript'') using various forms of ] to form the mature mRNA, which is then used as a template for protein synthesis by the ]. In ]s the mRNA may either be used as soon as it is produced, or be bound by a ribosome after having moved away from the ]. In contrast, ]s make mRNA in the ] and then translocate it across the ] into the ], where ] then takes place. The rate of protein synthesis is higher in prokaryotes than eukaryotes and can reach up to 20 amino acids per second.<ref name="Dobson">Dobson CM. (2000). The nature and significance of protein folding. In ''Mechanisms of Protein Folding'' 2nd ed. Ed. RH Pain. ''Frontiers in Molecular Biology'' series. Oxford University Press: New York, NY.</ref> | |||
| The process of synthesizing a protein from an mRNA template is known as ]. The mRNA is loaded onto the ribosome and is read three nucleotides at a time by matching each codon to its ]ing ] located on a ] molecule, which carries the amino acid corresponding to the codon it recognizes. The enzyme ] "charges" the tRNA molecules with the correct amino acids. The growing polypeptide is often termed the ''nascent chain''. Proteins are always biosynthesized from ] to ]. | |||
| The size of a synthesized protein can be measured by the number of amino acids it contains and by its total ], which is normally reported in units of ''daltons'' (synonymous with ]s), or the derivative unit kilodalton (kDa). ] proteins are on average 466 amino acids long and 53 kDa in mass.<ref name="Lodish" /> The largest known proteins are the ]s, a component of the ] ], with a molecular mass of almost 3,000 kDa and a total length of almost 27,000 amino acids.<ref>{{cite journal |author=Fulton A, Isaacs W |title=Titin, a huge, elastic sarcomeric protein with a probable role in morphogenesis |journal=Bioessays |volume=13 |issue=4 |pages=157–61 |year=1991 |pmid=1859393 | doi = 10.1002/bies.950130403 <!--Retrieved from CrossRef by DOI bot-->}}</ref> | |||
| ===Chemical synthesis=== | |||
| Short proteins can also be synthesized chemically by a family of methods known as ], which rely on ] techniques such as ] to produce peptides in high yield.<ref>{{cite journal |author=Bruckdorfer T, Marder O, Albericio F |title=From production of peptides in milligram amounts for research to multi-tons quantities for drugs of the future |journal=Curr Pharm Biotechnol |volume=5 |issue=1 |pages=29–43 |year=2004 |pmid=14965208 | doi = 10.2174/1389201043489620 <!--Retrieved from CrossRef by DOI bot-->}}</ref> Chemical synthesis allows for the introduction of non-natural amino acids into polypeptide chains, such as attachment of ] probes to amino acid side chains.<ref>{{cite journal |author=Schwarzer D, Cole P |title=Protein semisynthesis and expressed protein ligation: chasing a protein's tail |journal=Curr Opin Chem Biol |volume=9 |issue=6 |pages=561–9 |year=2005 |pmid=16226484 | doi = 10.1016/j.cbpa.2005.09.018 <!--Retrieved from CrossRef by DOI bot-->}}</ref> These methods are useful in laboratory ] and ], 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 ]. Most chemical synthesis methods proceed from C-terminus to N-terminus, opposite the biological reaction. | |||
| == Structure of proteins == | |||
| {{main|Protein structure}} | |||
| ]. 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 ] into unique 3-dimensional structures. The shape into which a protein naturally folds is known as its ]. Although many proteins can fold unassisted, simply through the chemical properties of their amino acids, others require the aid of molecular ]s to fold into their native states. Biochemists often refer to four distinct aspects of a protein's structure: | |||
| * '']'': the ] | |||
| * '']'': regularly repeating local structures stabilized by ]s. The most common examples are the ] and ].<ref name="Branden">Branden C, Tooze J. (1999). ''Introduction to Protein Structure'' 2nd ed. Garland Publishing: New York, NY</ref> Because secondary structures are local, many regions of different secondary structure can be present in the same protein molecule. | |||
| * '']'': the overall shape of a single protein molecule; the spatial relationship of the secondary structures to one another. Tertiary structure is generally stabilized by nonlocal interactions, most commonly the formation of a ], but also through ]s, hydrogen bonds, ]s, and even ]s. The term "tertiary structure" is often used as synonymous with the term ''fold''. The Tertiary structure is what controls the basic function of the protein. | |||
| * '']'': the shape or structure that results from the ] of more than one protein molecule, usually called '']s'' in this context, which function as part of the larger assembly or ]. | |||
| 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 "]s", and transitions between them are called ''conformational changes.'' Such changes are often induced by the binding of a ] molecule to an enzyme's ], or the physical region of the protein that participates in chemical catalysis. In solution all proteins also undergo variation in structure through thermal vibration and the collision with other molecules, see the animation on the right. | |||
| ] (IgG, an ]), ], ] (a hormone), ] (an enzyme), and ] (an enzyme).]] | |||
| Proteins can be informally divided into three main classes, which correlate with typical tertiary structures: ]s, ]s, and ]s. Almost all globular proteins are ] and many are enzymes. Fibrous proteins are often structural; membrane proteins often serve as ] or provide channels for polar or charged molecules to pass through the cell membrane. | |||
| A special case of intramolecular hydrogen bonds within proteins, poorly shielded from water attack and hence promoting their own ], are called ]s. | |||
| === 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 ] and ], both of which can produce information at ]ic resolution. ] is used to produce lower-resolution structural information about very large protein complexes, including assembled ]es;<ref name="Branden" /> a variant known as ] can also produce high-resolution information in some cases, especially for two-dimensional crystals of membrane proteins.<ref>Gonen T, Cheng Y, Sliz P, Hiroaki Y, Fujiyoshi Y, Harrison SC, Walz T. (2005). Lipid-protein interactions in double-layered two-dimensional AQP0 crystals. ''Nature'' 438(7068):633–8.</ref> Solved structures are usually deposited in the ] (PDB), a freely available resource from which structural data about thousands of proteins can be obtained in the form of ] for each atom in the protein. | |||
| 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 ], one of the major structure determination methods. In particular, globular proteins are comparatively easy to ] in preparation for X-ray crystallography. Membrane proteins, by contrast, are difficult to crystallize and are underrepresented in the PDB.<ref>Walian P, Cross TA, Jap BK. (2004). Structural genomics of membrane proteins ''Genome Biol'' 5(4): 215.</ref> ] initiatives have attempted to remedy these deficiencies by systematically solving representative structures of major fold classes. ] methods attempt to provide a means of generating a plausible structure for proteins whose structures have not been experimentally determined. | |||
| == Cellular functions == | |||
| {{Expand-section|Use of protein (especially the use in cell buffering agent)|date=March 2008}} | |||
| Proteins are the chief actors within the cell, said to be carrying out the duties specified by the information encoded in genes.<ref name="Lodish" /> With the exception of certain types of ], most other biological molecules are relatively inert elements upon which proteins act. Proteins make up half the dry weight of an '']'' cell, whereas other macromolecules such as DNA and RNA make up only 3% and 20%, respectively.<ref name="Voet">Voet D, Voet JG. (2004). ''Biochemistry'' Vol 1 3rd ed. Wiley: Hoboken, NJ.</ref> The set of proteins expressed in a particular cell or cell type is known as its ]. | |||
| ] is shown as a simple ball-and-stick molecular model. To scale in the top right-hand corner are two of its substrates, ] and ].]] | |||
| The chief characteristic of proteins that 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 ] 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 ] protein binds to human ] with a sub-femtomolar ] (<10<sup>-15</sup> M) but does not bind at all to its amphibian homolog ] (>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 ] specific to the amino acid ] discriminates against the very similar side chain of the amino acid ]. | |||
| 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 ]ize to form fibrils; this process occurs often in structural proteins that consist of globular monomers that self-associate to form rigid fibers. ]s also regulate enzymatic activity, control progression through the ], and allow the assembly of large ]es 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 ] networks. | |||
| ===Enzymes=== | |||
| {{main|Enzyme}} | |||
| The best-known role of proteins in the cell is as ]s, which ] 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 ], as well as manipulating DNA in processes such as ], ], and ]. Some enzymes act on other proteins to add or remove chemical groups in a process known as ]. About 4,000 reactions are known to be catalyzed by enzymes.<ref>{{cite journal|url=http://www.expasy.org/NAR/enz00.pdf|author= Bairoch A.|year= 2000|title= The ENZYME database in 2000 |journal=Nucleic Acids Res|volume=28|pages=304–305|pmid= 10592255 | doi = 10.1093/nar/28.1.304}}</ref> The rate acceleration conferred by enzymatic catalysis is often enormous - as much as 10<sup>17</sup>-fold increase in rate over the uncatalyzed reaction in the case of ] (78 million years without the enzyme, 18 milliseconds with the enzyme).<ref>{{cite journal |author=Radzicka A, Wolfenden R.|year= 1995|title= A proficient enzyme |journal= Science |volume=6 |issue=267 |pages=90–3| pmid=7809611|doi= 10.1126/science.7809611}}</ref> | |||
| The molecules bound and acted upon by enzymes are called ]s. 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 - 3-4 residues on average - that are directly involved in catalysis.<ref></ref> The region of the enzyme that binds the substrate and contains the catalytic residues is known as the ]. | |||
| ===Cell signaling and ligand binding=== | |||
| ] that binds a ] antigen.]] | |||
| Many proteins are involved in the process of ] and ]. Some proteins, such as ], are extracellular proteins that transmit a signal from the cell in which they were synthesized to other cells in distant ]. Others are ]s that act as ] 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 ] detected by other proteins within the cell. | |||
| ] are protein components of ] whose main function is to bind ]s, or foreign substances in the body, and target them for destruction. Antibodies can be ]d into the extracellular environment or anchored in the membranes of specialized ]s known as ]s. 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. | |||
| 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 ] 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 ], which transports ] from the ]s to other organs and tissues in all ]s and has close ]s in every biological ]. ] are sugar-binding proteins which are highly specific for their sugar moieties. ] typically play a role in biological ] phenomena involving cells and proteins. ]s and ]s are highly specific binding proteins. | |||
| ]s can also serve as ligand transport proteins that alter the ] of the cell membrane to small molecules and ions. The membrane alone has a ] core through which ] or charged molecules cannot ]. Membrane proteins contain internal channels that allow such molecules to enter and exit the cell. Many ] proteins are specialized to select for only a particular ion; for example, ] and ] channels often discriminate for only one of the two ions. | |||
| ===Structural proteins=== | |||
| Structural proteins confer stiffness and rigidity to otherwise-fluid biological components. Most structural proteins are ]s; for example, ] and ] are globular and soluble as monomers, but ]ize to form long, stiff fibers that comprise the ], which allows the cell to maintain its shape and size. ] and ] are critical components of ] such as ], and ] is found in hard or filamentous structures such as ], ], ]s, ], and some ]s. | |||
| Other proteins that serve structural functions are ]s such as ], ], and ], which are capable of generating mechanical forces. These proteins are crucial for cellular ] of single celled organisms and the ] of many sexually reproducing multicellular organisms. They also generate the forces exerted by contracting ]s. | |||
| == Methods of study == | |||
| {{main|Protein methods}} | |||
| As some of the most commonly studied biological molecules, the activities and structures of proteins are examined both '']'' and '']''. ''In vitro'' studies of purified proteins in controlled environments are useful for learning how a protein carries out its function: for example, ] studies explore the ] 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|Protein purification}} | |||
| In order to perform '']'' analysis, a protein must be purified away from other cellular components. This process usually begins with ], in which a cell's membrane is disrupted and its internal contents released into a solution known as a ]. The resulting mixture can be purified using ], which fractionates the various cellular components into fractions containing soluble proteins; membrane ]s and proteins; cellular ]s, and ]s. ] by a method known as ] can concentrate the proteins from this lysate. Various types of ] are then used to isolate the protein or proteins of interest based on properties such as molecular weight, net charge and binding affinity. The level of purification can be monitored using various types of ] if the desired protein's molecular weight and ] are known, by ] if the protein has distinguishable spectroscopic features, or by ]s if the protein has enzymatic activity. Additionally, proteins can be isolated according their charge<ref></ref> using ]. | |||
| For natural proteins, a series of purification steps may be necessary to obtain protein sufficiently pure for laboratory applications. To simplify this process, ] 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 ] residues (a "]"), is attached to one terminus of the protein. As a result, when the lysate is passed over a chromatography column containing ], the histidine residues ligate the nickel and attach to the column while the untagged components of the lysate pass unimpeded. | |||
| ===Cellular localization=== | |||
| ]s and structures tagged with ] (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 ] and membrane-bound or secreted proteins in the ], the specifics of how proteins are ] 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 ] or ] consisting of the natural protein of interest linked to a "]" such as ] (GFP). The fused protein's position within the cell can be cleanly and efficiently visualized using ], as shown in the figure opposite. In these cases, additional fluorescent chimeric proteins are generally required to prove the inferred localization. | |||
| 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, ] will allow for fluorescence colocalization and demonstration of location. Fluorescent dyes are used to label cellular compartments for a similar purpose. | |||
| Other possibilities exist, as well. For example, ] 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 ]. 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 ]. 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. | |||
| Through another genetic engineering application known as ], researchers can alter the protein sequence and hence its structure, cellular localization, and susceptibility to regulation, which can be followed ''in vivo'' by GFP tagging or ''in vitro'' by ] and binding studies. | |||
| ===Proteomics and bioinformatics=== | |||
| {{main|Proteomics|Bioinformatics}} | |||
| The total complement of proteins present at a time in a cell or cell type is known as its ], and the study of such large-scale data sets defines the field of ], named by analogy to the related field of ]. Key experimental techniques in proteomics include ], which allows the separation of a large number of proteins, ], which allows rapid high-throughput identification of proteins and sequencing of peptides (most often after ]), ]s, which allow the detection of the relative levels of a large number of proteins present in a cell, and ], which allows the systematic exploration of ]s. The total complement of biologically possible such interactions is known as the ]. A systematic attempt to determine the structures of proteins representing every possible fold is known as ]. | |||
| The large amount of genomic and proteomic data available for a variety of organisms, including the ], allows researchers to efficiently identify ] proteins in distantly related organisms by ]. ]s can perform more specific sequence manipulations such as ] maps, ] analyses for ] sequences, and ] prediction. From this data ]s can be constructed and ]ary hypotheses developed using special software like ] regarding the ancestry of modern organisms and the genes they express. The field of ] seeks to assemble, annotate, and analyze genomic and proteomic data, applying ] techniques to biological problems such as ] and ]. | |||
| ===Structure prediction and simulation=== | |||
| Complementary to the field of structural genomics, ] seeks to develop efficient ways to provide plausible models for proteins whose structures have not yet been determined experimentally <ref name="zhang2008">{{cite journal |author=Zhang Y |title=Progress and challenges in protein structure prediction |journal=Curr Opin Struct Biol |volume=18 |issue=3 |pages=342-348 |year=2008 |id={{Entrez Pubmed|18436442}} |doi=10.1016/j.sbi.2008.02.004 |pmid=18436442}}</ref>. The most successful type of structure prediction, known as ], 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. 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.<ref name="Zhang">Zhang Y, Skolnick J. (2005). The protein structure prediction problem could be solved using the current PDB library. ''Proc Natl Acad Sci USA'' 102(4):1029–34.</ref> Many structure prediction methods have served to inform the emerging field of ], in which novel protein folds have already been designed.<ref name="Kuhlman">Kuhlman B, Dantas G, Ireton GC, Varani G, Stoddard BL, Baker D. (2003). Design of a novel globular protein fold with atomic-level accuracy. ''Science'' 302(5649):1364–8.</ref> A more complex computational problem is the prediction of intermolecular interactions, such as in ] and ]. | |||
| The processes of protein folding and binding can be simulated using techniques derived from ], which increasingly take advantage of ] as in the ] project. The folding of small alpha-helical protein domains such as the ] headpiece<ref name="Zagrovic">Zagrovic B, Snow CD, Shirts MR, Pande VS. (2002). Simulation of folding of a small alpha-helical protein in atomistic detail using worldwide-distributed computing. ''J Mol Biol'' 323(5):927–37.</ref> and the ] accessory protein<ref name="Herges">Herges T, Wenzel W. (2005). In silico folding of a three helix protein and characterization of its free-energy landscape in an all-atom force field. ''Phys Rev Let'' 94(1):018101.</ref> have been successfully simulated ''in silico'', and hybrid methods that combine standard molecular dynamics with ] calculations have allowed exploration of the electronic states of ]s.<ref name="Hoffmann">Hoffmann M, Wanko M, Strodel P, Konig PH, Frauenheim T, Schulten K, Thiel W, Tajkhorshid E, Elstner M. (2006). Color tuning in rhodopsins: the mechanism for the spectral shift between bacteriorhodopsin and sensory rhodopsin II. ''J Am Chem Soc'' 128(33):10808-18. </ref> | |||
| ==Nutrition== | |||
| {{further|]}} | |||
| Most ]s and plants can biosynthesize all 20 standard ], while animals (including humans) must obtain some of the amino acids from the ].<ref name="Voet" /> | |||
| The amino acids that an organism cannot synthesize on its own are referred to as ]. Key enzymes that synthesize certain amino acids are not present in animals - such as ], which catalyzes the first step in the synthesis of ], ], and ] from ]. 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 broken down through ], which typically involves ] of the protein through exposure to ] and ] by enzymes called ]s. Some ingested amino acids are used for protein biosynthesis, while others are converted to ] through ], or fed into the ]. This use of protein as a fuel is particularly important under ] conditions as it allows the body's own proteins to be used to support life, particularly those found in ].<ref>{{cite journal |author=Brosnan J |title=Interorgan amino acid transport and its regulation |url=http://jn.nutrition.org/cgi/content/full/133/6/2068S |journal=J Nutr |volume=133 |issue=6 Suppl 1 |pages=2068S–72S |year=2003 |pmid=12771367}}</ref> Amino acids are also an important dietary source of ]. | |||
| == History == | |||
| {{further|]}} | |||
| Proteins were recognized as a distinct class of biological molecules in the eighteenth century by ] and others, distinguished by the molecules' ability to ] or ] under treatments with heat or acid. Noted examples at the time included albumin from ]s, ], ], ], and wheat ]. Dutch chemist ] carried out ] of common proteins and found that nearly all proteins had the same ]. The term "protein" to describe these molecules was proposed in 1838 by Mulder's associate ]. Mulder went on to identify the products of protein degradation such as the ] ] for which he found a (nearly correct) molecular weight of 131 ]. | |||
| 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 ], ], various ]s, and digestive/metabolic enzymes obtained from ]s. In the late 1950s, the ] purified 1 kg (= one million milligrams) of pure bovine pancreatic ] and made it freely available to scientists around the world. | |||
| ] is credited with the successful prediction of regular protein ]s based on ], an idea first put forth by ] in 1933. Later work by ] on ], based partly on previous studies by ], contributed an understanding of ] and structure mediated by ]. In 1949 ] correctly determined the amino acid sequence of ], thus conclusively demonstrating that proteins consisted of linear polymers of amino acids rather than branched chains, ]s, or ]s. The first atomic-resolution structures of proteins were solved by ] in the 1960s and by ] in the 1980s. As of 2006, the ] has nearly 40,000 atomic-resolution structures of proteins. In more recent times, ] of large macromolecular assemblies and computational ] of small protein ] are two methods approaching atomic resolution. | |||
| == See also == | |||
| <div style="-moz-column-count:4; column-count:4;"> | |||
| * ] | |||
| * ] | |||
| * ] | |||
| * ] | |||
| * ] | |||
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| </div> | |||
| ==References== | |||
| {{reflist|2}} | |||
| == External links == | |||
| * , 'When a "tape" of mRNA passes through the "playing head" of a ribosome, the "notes" produced are amino acids and the pieces of music they make up are proteins.' | |||
| * , also called "Proteins: Structure, Function, and Bioinformatics" and previously "Proteins: Structure, Function, and Genetics" (1986–1995). | |||
| ===Databases and projects=== | |||
| * curates protein-chemical interactions, as well as gene/protein-disease relationships and chemical-disease relationships. | |||
| * A Meta search engine (29 databases) for gene and protein information. | |||
| * (see also , presenting short accounts on selected proteins from the PDB) | |||
| * : rotatable, zoomable 3D model with wiki annotations for every known protein molecular structure. | |||
| * | |||
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| ===Tutorials and educational websites=== | |||
| * | |||
| * | |||
| * - Home Page for Learning Environmental Chemistry | |||
| {{Protein topics}} | |||
| {{Protein methods}} | |||
| {{Enzymes}} | |||
| {{Cytoskeletal Proteins}} | |||
| {{Coagulation}} | |||
| {{Complement system}} | |||
| {{Carrier proteins}} | |||
| {{Food chemistry}} | |||
| {{Protein metabolism}} | |||
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