Protein carboxyl methyltransferase selectively modifies an atypical form of calmodulin. Evidence for methylation at deamidated asparagine residues.
Prolonged incubation of native bovine brain calmodulin with S-adenosyl-L-[methyl-3H]methionine and protein carboxyl methyltransferase results in maximal methylation of only 1-2% of the calmodulin molecules. In contrast, calmodulin which has been subjected to a prior alkaline treatment (0.1 M NH4OH, 37 degrees C for 3 h) can be methylated to a level of 30-50%. This treatment is known to be effective in deamidating certain asparagine residues which lie in unstable sequences, particularly -Asn-Gly- sequences. Bovine brain calmodulin has three such sequences (Watterson, D. M., Sharief, F., and Vanaman, T. C. (1980) J. Biol. Chem. 255, 962-975). The enhancement of methylation by alkaline treatment is substantially reduced if calmodulin is first reacted with bis-(I,I-trifluoroacetoxy)iodobenzene, a reagent which converts the carboxamide group of asparagine and glutamine residues to the corresponding primary amines. Thus, protein carboxyl methyltransferase selectively modifies an abnormal form of calmodulin that is probably deamidated. These findings suggest that protein carboxyl methylation may play a role in the disposition of abnormal proteins which contain atypical, isomerized aspartyl residues arising via spontaneous deamidation of unstable asparagines.
D000818:Animals; D001216:Asparagine; D001921:Brain / Q000201:enzymology*; D002147:Calmodulin / Q000378:metabolism*; D002417:Cattle; D004591:Electrophoresis, Polyacrylamide Gel; D006863:Hydrogen-Ion Concentration; D007525:Isoelectric Focusing; D007527:Isoenzymes / Q000378:metabolism; D007700:Kinetics; D008745:Methylation; D008970:Molecular Weight; D011496:Protein Methyltransferases / Q000378:metabolism*; D011497:Protein O-Methyltransferase / Q000378:metabolism*; D012436:S-Adenosylmethionine / Q000378:metabolism
D002147:Calmodulin; D007527:Isoenzymes; D001216:Asparagine; D012436:S-Adenosylmethionine; D011496:Protein Methyltransferases; D011497:Protein O-Methyltransferase