Specific recognition of calmodulin from Dictyostelium discoideum by the ATP, ubiquitin-dependent degradative pathway

Calmodulin purified from Dictyostelium discoideum is selectively degraded by rabbit reticulocyte extracts in the presence of ubiquitin and ATP. This protein forms a 1:1 covalent conjugate with ubiquitin. Analyses of the cyanogen bromide fragments of the protein conjugate indicate that lysine 115 on calmodulin is the ubiquitin conjugation site. Bovine brain calmodulin which contains a trimethyllysine residue at this position is not a substrate for conjugation with ubiquitin, and its degradation rate is not affected by ATP and ubiquitin. These results suggest that the trimethyllysine residue in mammalian calmodulin may function in protecting the protein from degradation by the ATP, ubiquitin-dependent pathway. Since there are eight lysine residues in Dictyostelium calmodulin, the specific conjugation of ubiquitin to lysine 115 may provide a good model system to delineate the structural features required for the conjugation and to follow the degradative steps in the pathway.