Posttranslational modification of proteins

Proteins are the workhorses of the cell, performing most of the reactions for the cell to carry out its daily function. The size of a protein can range from 70 amino acids to subunits as large as 15 000 amino acids roughly ranging in molecular weight from 7 kD to 1.7 MDa. Since the genome contains 30 000 genes, there exists at least an identical number of proteins. Covalent posttranslational modifications are the methods that the cells utilize to diversify the limited number of proteins that can be generated, altering the activity and functions of the proteins. A posttranslational modification is, as suggested, a modification to a protein after its translation from messenger ribonucleic acid (mRNA) to its specific sequence, transforming the 20 natural amino acids found in the body into a much more diversified collective. Shown in Table 1 is a list of posttranslational modifications and the residues onto which they occur. It is important to point out that there are no known modifications to alanine, isoleucine, leucine, phenylalanine, and valine side chains. The most common posttranslational modifications, discussed in the following sections, include phosphorylation, sulfation, disulfide formation, N-methylation, O-methylation, S-methylation, N-acetylation, hydroxylation, glycosylation, ADP-ribosylation, prenylation, biotinylation, lipoylation, and phosphopantetheine tethering. Many of the posttranslational modifications are proven to be cross talks.^1,2 Other modifications exist in a smaller extent and include oxidation of methionine, C-methylation, ubiquitylation, carboxylation, and amidation. These topics will not be covered in this chapter which is meant to focus primarily on the recent literature (2005....