Structural and Functional Aspect of Protein Folding
written by: Rishi Prakash•edited by: DaniellaNicole•updated: 8/17/2010
Proteins formed during the translational process are require to go through various post-translational modifications to make them functional. Learn the mechanisms that take place during protein folding and processing.
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Protein synthesis takes place by the process called translation. It occurs in the cytoplasm where ribosomes act as a substrate molecule and aminoacetyl t-RNA and mRNA containing anticodon and codon complex forms a long chain of polypeptide. There are 4 basic steps involved in translation including 1. Binding of an incoming aminoacyl-tRNA, 2. Peptide bond formation, 3. Translocation, 4. Termination of polypeptide synthesis.
In addition, there is a fifth and final step involved in protein synthesis i.e., folding and processing. The newly formed polypeptide chain is folded and processed into its biologically active form. During or after its synthesis, the polypeptide gradually assumes its native conformation, with the development of correct hydrogen bonds and van der Walls, ionic and hydrophobic interactions. In this way the linear or one-dimensional genetic message in the mRNA is converted into the three dimensional structure of the protein. Some newly formed proteins in both prokaryotes and eukaryotes, do not attain their final biologically active conformation until they have been altered by one or more processing reactions called post-translational modifications
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Different Aspects of Post-translational Modifications:
Amino Terminal and Carboxyl-Terminal Modifications: Initially, all polypeptides begin with a residue of N-formylmethionine in bacteria and methionine in eukaryotes. However, the formyl group, the amino-terminal Met residue and often additional amino terminal residues may be removed enzymatically and thus do not appear in the final functional protein.
Modification of Individual Amino Acids: The hydroxyl group of certain Ser, Thr, and Tyr residues of some proteins are enzymatically phosphorylated by ATP. The phosphate group adds negative charges to these polypeptides. The functional significance of this modification varies from one protein to the next.
Attachment of Carbohydrate Side Chains: The carbohydrate side chains of glycoproteins are attached covalently during or after the synthesis of the polypeptide. In some glycoproteins, the carbohydrate side chain attached enzymatically to Asn residues, in others to Ser or Thr residues. Many proteins that function extrcellularly, as well as the lubricating proteoglycans that coat mucous membranes contain oligosaccaride side chains.
Addition of Prosthetic Group: Several prokaryotic and eukaryotic proteins require covalently bound prosthetic groups to perform their activities. Examples are biotin molecules of acetyl-CoA carboxylase and the heme group of cytochrome c.
Proteolytic Processing: Many proteins are initially synthesized as large, inactive precursor proteins that are proteolytically trimmed to produce their smaller, active forms. Examples are insulin, some vital proteins and proteases such as trypsin and chymotypsin.
Formation of Disulphide Cross Links: After folding into their native conformations, some proteins form interchain or intrachain disulfide bridges between Cys residues. Disulfide bonds are common in proteins to be exported from eukayotic cells. The cross-links formed in this way help to protect the native conformation of the protein molecule from denaturation in an extra cellular environment that can differ greatly from intracellular conditions and is generally oxidizing.