Some animal viruses, notably HIV, poliovirus, and hepatitis virus, synthesize long polycistronic proteins from one long mRNA molecule. The viral protein molecules translated from these long mRNAs are subsequently cleaved at defined sites to provide the several specific viral proteins required for viral function. In animal cells, many cellular proteins are synthesized from the mRNA template as a precursor molecule, which then must be modified to achieve the active protein. The prototype is insulin, a small protein having two polypeptide chains with interchain and intrachain disulfide bridges. The molecule is synthesized as a single chain precursor, orprohormone, which folds to allow the formation of specific, intra- or intermolecular disulfide bridges. A specific protease then clips out the segment that connects the two chains which form the functional insulin molecule.
Many other peptides are synthesized as precursor pro proteins that require modifications before attaining biologic activity. Many of the posttranslational modifications involve the removal of amino terminal amino acid residues by specific aminopeptidases. By contrast, collagen, an abundant protein in the extracellular spaces of higher eukaryotes, is synthesized as procollagen. Three procollagen poly peptide molecules, frequently not identical in sequence, align themselves in a particular way that is dependent on the existence of specific amino terminal peptides.
Specific enzymes then carry out hydroxylations and oxidations of specific amino acid residues within the procollagen molecules to provide cross-links for greater stability. Amino terminal peptides are cleaved off the molecule to form the final product—a strong, insoluble collagen molecule. Many other posttranslational modifications of proteins occur. Covalent modification by acetylation, phosphorylation, methylation, ubiquitylation, and glycosylation is common.
