Fundamentals of Biochemistry - Filippovich Yu. B. 1999

Protein Metabolism
Post-translational Protein Modification

It should not be assumed that all Proteins produced via ribosomal synthesis immediately possess a fully mature Structure. In many cases, they are synthesized as precursors and only acquire their final conformation following the proteolytic Cleavage of a peptide fragment. Examples of such post-translational modification include the removal of signal Peptides upon completion of protein translocation across Introduction/36.html">Biological Membranes (see Fig. 101), the Fragmentation of Protein precursors to yield functionally active proteins—such as The conversion of trypsinogen to Trypsin or proinsulin to Insulin—or biologically active peptides like Hormones and releasing factors. A similar mechanism underlies the post-translational modification involving the proteolytic Cleavage of the N-terminal formylmethionine or Methionine residue, which, as noted above, initiates the assembly of polypeptide chains during ribosomal Protein Synthesis.

At the same time, post-translational modifications involving amino acid side chains are widespread. These include: the hydroxylation of Proline residues during the conversion of procollagen to Collagen; the Acetylation of the N-terminal amino acid in protein molecules, as seen, for example, in The Biosynthesis of egg albumin; the methylation of Lysine and Arginine residues mediated by S-adenosyl-L-methionine protein N-methyl- or O-methyltransferases, which is particularly prevalent in the post-translational modification of Histones, non-histone Nuclear Proteins, and ribosomal proteins; the attachment of oligosaccharide chains to asparagine, Serine, and Threonine residues during glycoprotein biosynthesis; the amidation of aspartic and glutamic acid residues, which is currently linked to protein heterogeneity during ontogeny and Aging; the carboxylation of glutamic acid residues at the y-carbon atom, resulting in The formation of y-Carboxyglutamic acid residues essential, inter alia, for binding Ca²⁺; and the adenylylation and uridylylation of Tyrosine residues. Phosphorylation of histones and non-histone Chromatin proteins is another post-translational process of critical importance for regulating the METABOLIC ACTIVITY OF The Genome. An example of co-translational protein modification is shown in Fig. 102.

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Fig. 101. Protein translocation across a lipoprotein membrane:

A — co-translational protein transport; B — post-translational protein transport. The signal peptide interacts with a membrane receptor, facilitating the insertion of the newly synthesized ribosomal protein into the lipoprotein membrane.

In the case of co-translational transport, the ribosome is also anchored to the membrane via a specific receptor, while protein translocation itself is driven by the formation of a polypeptide chain conformer. During post-translational transport, translocation involves protein factors adjacent to the signal peptide receptors. In both instances, the signal peptide is cleaved from the functional portion of the protein by a signal peptidase; its ultimate fate remains to be elucidated.