Protein



 

Proteins are large post-translational modification: either before the protein can function in the cell, or as part of control mechanisms. Proteins can also work together to achieve a particular function, and they often associate to form stable complexes.

Like other biological metabolism.

The word protein comes from the Greek πρώτα ("prota"), meaning "of primary importance" and these molecules were first described and named by the Swedish chemist Nobel Prize in Chemistry for their discoverers.

Biochemistry

Main articles: peptide bond

 

 

Proteins are linear polymers built from 20 different L-α-dihedral angles 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 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, conformation.

Synthesis

Main article: Protein biosynthesis

  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 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.[6]

The process of synthesizing a protein from an mRNA template is known as 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.

The size of a synthesized protein can be measured by the number of amino acids it contains and by its total 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.[7]

Chemical synthesis

Short proteins can also be synthesized chemically by a family of methods known as tertiary structure. Most chemical synthesis methods proceed from C-terminus to N-terminus, opposite the biological reaction.

Structure of proteins

Main article: Protein structure

  Most proteins chaperones to efficiently fold to their native states. Biochemists often refer to four distinct aspects of a protein's structure:

  Proteins are not entirely rigid molecules. In addition to these levels of structure, proteins may shift between several related structures while they perform their biological function. 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 all proteins also undergo variation in structure through thermal vibration and the collision with other molecules, see the animation on the right.

  Proteins can be informally divided into three main classes, which correlate with typical tertiary structures: receptors 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 dehydrons.

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 electron crystallography can also produce high-resolution information in some cases, especially for two-dimensional crystals of membrane proteins.[11] 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.

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 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.[5] With the exception of certain types of proteome.

 

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 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 isoleucine.

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 signaling networks.

Enzymes

Main article: Enzyme

The best-known role of proteins in the cell is their duty as post-translational modification. About 4,000 reactions are known to be catalyzed by enzymes.[14] 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).[15]

The molecules bound and acted upon by enzymes are known as 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 - 3-4 residues on average - that are directly involved in catalysis.[16] The region of the enzyme that binds the substrate and contains the catalytic residues is known as the active site.

Cell signaling and Ligand transport

  Many proteins are involved in the process of 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.

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.

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 oxygen from the lungs to other organs and tissues in all vertebrates and has close homologs in every biological kingdom.

sodium 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 fibrous proteins; for example, 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.

Other proteins that serve structural functions are dynein, which are capable of generating mechanical forces. These proteins are crucial for cellular motility of single-celled organisms and the sperm of many sexually reproducing multicellular organisms. They also generate the forces exerted by contracting muscles.

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, 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 electrofocusing.

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 nickel, the histidine residues ligate the nickel and attach to the column while the untagged components of the lysate pass unimpeded.

Cellular localization

  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 green fluorescent protein (GFP). The fused protein's position within the cell can be cleanly and efficiently visualized using microscopy, as shown in the figure opposite.

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, which can be followed in vivo by GFP tagging or in vitro by enzyme kinetics and binding studies.

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 protein-protein interactions. The total complement of biologically possible such interactions is known as the interactome. A systematic attempt to determine the structures of proteins representing every possible fold is known as structural genomics.

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 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

Complementary to the field of structural genomics, protein-protein interaction prediction.

The processes of protein folding and binding can be simulated using techniques derived from rhodopsins.[22]

Nutrition

Further information: Protein in nutrition

Most essential amino acids. 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 nitrogen.

History

Further information: History of molecular biology

Proteins were recognized as a distinct class of biological molecules in the eighteenth century by Da.

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, ribonuclease A and made it freely available to scientists around the world.

domains are two methods approaching atomic resolution.

See also

References

  1. ^ Sumner, JB (1926). "The Isolation and Crystallization of the Enzyme Urease. Preliminary Paper". J Biol Chem 69: 435-41.
  2. ^ Muirhead H, Perutz M (1963). "Structure of hemoglobin. A three-dimensional fourier synthesis of reduced human hemoglobin at 5.5 A resolution". Nature 199 (4894): 633-8. PMID 14074546.
  3. ^ Kendrew J, Bodo G, Dintzis H, Parrish R, Wyckoff H, Phillips D (1958). "A three-dimensional model of the myoglobin molecule obtained by x-ray analysis". Nature 181 (4610): 662-6. PMID 13517261.
  4. ^ Nelson, D. L. and Cox, M. M. (2005) Lehninger's Principles of Biochemistry, 4th Edition, W. H. Freeman and Company, New York.
  5. ^ a b c 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.
  6. ^ 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.
  7. ^ Fulton A, Isaacs W (1991). "Titin, a huge, elastic sarcomeric protein with a probable role in morphogenesis". Bioessays 13 (4): 157-61. PMID 1859393.
  8. ^ Bruckdorfer T, Marder O, Albericio F (2004). "From production of peptides in milligram amounts for research to multi-tons quantities for drugs of the future". Curr Pharm Biotechnol 5 (1): 29-43. PMID 14965208.
  9. ^ Schwarzer D, Cole P (2005). "Protein semisynthesis and expressed protein ligation: chasing a protein's tail". Curr Opin Chem Biol 9 (6): 561-9. PMID 16226484.
  10. ^ a b Branden C, Tooze J. (1999). Introduction to Protein Structure 2nd ed. Garland Publishing: New York, NY
  11. ^ 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.
  12. ^ Walian P, Cross TA, Jap BK. (2004). Structural genomics of membrane proteins Genome Biol 5(4): 215.
  13. ^ a b Voet D, Voet JG. (2004). Biochemistry Vol 1 3rd ed. Wiley: Hoboken, NJ.
  14. ^ Bairoch A. (2000). "The ENZYME database in 2000". Nucleic Acids Res 28: 304-305. PMID 10592255.
  15. ^ Radzicka A, Wolfenden R. (1995). "A proficient enzyme.". Science 6 (267): 90-931. PMID 7809611.
  16. ^ The Catalytic Site Atlas at The European Bioinformatics Institute
  17. ^ Calculating protein charge (isoelectric point)
  18. ^ 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.
  19. ^ 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.
  20. ^ 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.
  21. ^ 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.
  22. ^ 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.
  23. ^ Brosnan J (2003). "Interorgan amino acid transport and its regulation". J Nutr 133 (6 Suppl 1): 2068S-72S. PMID 12771367.

Databases and projects

  • The Protein Databank (see also PDB Molecule of the Month, presenting short accounts on selected proteins from the PDB)
  • Proteopeida - Life in 3D
  • UniProt the Universal Protein Resource
  • Human Protein Atlas
  • iHOP - Information Hyperlinked over Proteins
  • MIT's Laboratory for Protein Molecular Self-Assembly
  • NCBI Entrez Protein database
  • NCBI Protein Structure database
  • Human Protein Reference Database
  • Human Proteinpedia
  • Folding@Home (Stanford University)

Tutorials and educational websites

  • Proteins: Biogenesis to Degradation - The Virtual Library of Biochemistry and Cell Biology
  • Amino acid metabolism
  • Data Book of Molecules - Home Page for Learning Environmental Chemistry
v • d • e
Proteins

Proteasome Globular protein - Fibrous protein

v • d • e
Proteins: key Protein assay - Secretion assay
v • d • e
Proteins: EC number
list
v • d • e
Proteins of the Vinculin
v • d • e
Proteins: α2-macroglobulin - TAFI
v • d • e
Proteins: CD18 - Anaphylatoxin (C3a, C5a)
v • d • e
Proteins: carrier proteins
HormoneFollistatin - Growth hormone binding protein - Insulin-like growth factor binding protein - Neurophysins (Neurophysin I, II)
Membrane transport protein
v • d • e
Vitamins • Water
v • d • e
Protein Pyrimidine metabolism
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Protein". A list of authors is available in Wikipedia.