Protein post-translational cleavage

Protease is responsible for cleaving these precursor molecules to produce the final structural proteins of the mature virion core. By preventing post-translational cleavage of the Gag-Pol polyprotein, protease inhibitors (Pis) prevent the processing of viral proteins into functional conformations, resulting in the production of immature, noninfectious viral particles (Figure 49-4). Protease inhibitors are active against both HIV-1 and HIV-2 unlike the NRTTs, however, they do not need intracellular activation. 

In eukaryotes, each mRNA is monocistronic, that is, discounting any subsequent post-translational cleavage reactions that may occur, the mRNA encodes a single protein. In prokaryotes, many mRNAs are polycistronic, that is they encode several proteins. Each coding sequence in a prokaryotic mRNA has its own initiation and termination codons. 

Another general role of post-translational cleavage of polypeptide chains in viral systems is the specific processing of structural proteins leading to the assembly of the virus (44,45). In this respect, the semliki-Forest virus may be considered as an interesting model to find out how proteins which have different cellular locations reach their final sites within the cell. A single messenger RNA directs the synthesis of the viral capsid protein and of two membrane proteins. 

Scott, M.P. R. Jung K. Muntz N.C. Nielsen. A protease responsible for post-translational cleavage of a conserved Asn-Gly linkage in glycinin, the major seed storage protein of soybean. Proc. National Acad. Sci. 1992, 89, 658-662. 

Figure 7.35. Human prion protein single residue hydrophobicity plot. Arrows separated by bar indicate 55 residue sequence that completely forms a P-sheet. Open arrows indicate normal post-translational cleavage sites. Lower arrows indicate...

Compared to the genome, the proteome (the entire diverse protein content of a cell) is a far more dynamic system. Proteins imdergo post-translational modifications such as phosphorylation, glycosylation and sulphation, as well as cleavage for specific proteins. These alterations determine protein activity, localisation and turnover. All are subject to change following a toxic insult and, in some ways, the study of proteins holds more promise than the study of gene expression as the former is nearer to key activities in the cell. 

Post-translational modifications were recognized as additional sources of the structural modification of proteins.(22) Should such a modification occur by an enzyme-mediated process, as had been established for oxidation of sulfhydryl groups or the addition of carbohydrate or phosphate groups, or by the cleavage of the polypeptide with loss of a terminal amino group, or a larger part of the chain, it too could be subject to genetic variation. 

In order to assign the disulfide bonds of these molecules fast atom bombardment mass spectrometry (FABMS) which has been used not only to confirm amino acid sequence data but also to elucidate post-translational modifications of proteins, such as disulfide bonds, has been employed. For this purpose a sample of native Er-2, containing four methionines, was subjected to CNBr cleavage and without further fractionation directly... 

Proteins are typically made as pro-proteins and are then subsequently modified by post-translational processing involving selective proteolysis ( trimming ) and addition of other groups. Thus, nascent polypeptides commence with N-formylmethionine (bacteria) or methionine (eukaryotes). However, N-terminal sequences are often removed in proteolytic processing. In many eukaryote proteins, the final N-terminal amino acid of the processed protein is N-acetylated. The C-terminus may also be changed by peptide cleavage and other covalent modification. 

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