Homologous Methylated and Nonmethylated Histidine Peptides in Skeletal and Cardiac Myosins

Abstract Two tridecapeptides containing nonmethylated histidine residues have been isolated from tryptic digests of rabbit and bovine cardiac myosins with the following sequences, respectively: Leu-Leu-Ser-Ser-Leu-Asp-Ile-Asp-His-Gln-Asn-Tyr-Lys; Leu-Leu-Gly-Ser-Leu-Asp-Ile-Asp-His-Gln-Asn-Tyr-Lys. The peptides are homologous to the peptide containing 3-methylhistidine from rabbit skeletal muscle myosin (Huszar, G., and Elzinga, M. (1971) Biochemistry, 10, 229). There are four differences in the sequences of the rabbit skeletal and rabbit cardiac myosin peptides: Gly → Ser; Ile → Leu; Val → Ile; Thr → Asn. There is one difference in sequence between the cardiac peptides from rabbit and calf (Ser → Gly), indicating that this particular region of the primary structure of the myosin molecule is more similar in sequence in the same tissue from two different species than in heart and skeletal muscle of rabbit. All the amino acid replacements in the peptides are conservative and can be ascribed to single base changes. Based on the differences in the sequences of the cardiac histidine and skeletal 3-methylhistidine peptides from rabbit, it can be concluded that cardiac and skeletal myosin are synthesized under the control of different genes. The presence of nonmethylated histidine in cardiac myosins and the very conservative nature of the amino acid replacements around the histidine and 3-methylhistidine in cardiac and skeletal muscle myosins suggest to us that the lack of methylation is due to the absence of a histidine-methylating enzyme in cardiac muscle.