Les protéine carboxyle méthyltransférases des eucaryotes : deux classes distinctes d'enzymes

Abstract

Protein carboxyl methyltransferases are ubiquitous enzymes that transfer a methyl group from S-adenosyl-L-methionine (AdoMet) to some carboxyl groups of proteins. In eukaryotic cells, two distinct classes of these enzymes have been described to date. One of these, L-isoaspartate/D-aspartate methyltransferases, recognizes with high affinity damaged aspartic acid residues that originate mainly from spontaneous deamidation of asparagine residues and from racemisation of aspartate residues. These enzymes exist as molecular species of 27 kDa and a number of isoforms have been identified. In all cases, these enzymes are non-specific and the methyl esters formed by their action are highly sensitive to moderate alkaline conditions. Numerous studies have suggested that these enzymes may be involved in the repair of the altered residues, as reflected by the repair of various isoaspartate-containing peptides and some proteins following incubation with AdoMet and purified carboxyl methyltransferases. The other class of methyltransferases, the C-terminal carboxyl methyltransferases, catalyze the methylation of the carboxyl group of isoprenylated cysteine residues located in the C-terminal portion of various proteins, including members of the Ras superfamily of GTP-binding proteins. The post-translational modification of these proteins by isoprenylation and carboxyl methylation is supposed to play a major role in their association with cellular membranes, where they become physiologically active. In addition, recent studies have suggested that the methylation of isoprenylated proteins may play an important function in promoting specific interactions between these proteins and specific effectors located in the membrane.