Methylation at D-aspartyl residues in erythrocytes: possible step in the repair of aged membrane proteins.
Reversibly methylated aspartyl residues in human erythrocyte membrane proteins are shown to be in the "unnatural" D configuration. This is demonstrated by treatment of proteolytically derived aspartic acid beta-[3H]methyl ester with L- and D-amino-acid oxidases and by the resolution of diastereomeric L-leucyl dipeptides containing either L- or D-aspartic acid beta-methyl ester by ion-exchange chromatography. Based on this observation, we propose a novel role for eukaryotic protein carboxyl methyltransferases (protein O-methyltransferase; S-adenosyl-L-methionine:protein O-methyltransferase, EC 2.1.1.24). We suggest that these widely distributed enzymes function to recognize aspartyl residues that have racemized spontaneously for a subsequent repair reaction. This repair function is postulated to couple ester hydrolysis with the restoration of the original L configuration of the aspartyl residue. It is possible that similar types of racemization repair processes may occur by reversible covalent modifications at other residues. Other possible functions for D-aspartic acid beta-methyl ester residues in proteins are considered.
D000594:Amino Acid Oxidoreductases; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000032:analysis; D003605:D-Amino-Acid Oxidase; D004905:Erythrocyte Aging; D004910:Erythrocyte Membrane / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000097:blood*; D008745:Methylation; D016202:N-Methylaspartate
D008565:Membrane Proteins; D001224:Aspartic Acid; D016202:N-Methylaspartate; D000594:Amino Acid Oxidoreductases; D003605:D-Amino-Acid Oxidase