Apocalmodulin and Ca2+ calmodulin bind to the same region on the skeletal muscle Ca2+ release channel

The skeletal muscle Ca2+ release channel (RYR1) is regulated by calmodulin in both its Ca2+-free (apocalmodulin) and Ca2+-bound (Ca2+ calmodulin) stat es. Apocalmodulin is an activator of the channel, and Ca2+ calmodulin is an inhibitor of the channel. Both apocalmodulin and Ca2+ calmodulin binding s ites on RYR1 are destroyed by a mild tryptic digestion of the sarcoplasmic reticulum membranes, but calmodulin (either form), bound to RYR1 prior to t ryptic digestion, protects both the apocalmodulin and Ca2+ calmodulin sites from tryptic destruction. The protected sites ars after arginines 3630 and 3637 on RYR1. These studies suggest that both Ca2+ calmodulin and apocalmo dulin bind to the same or overlapping regions on RYR1 and block access of t rypsin to sites at amino acids 3630 and 3637. This sequence is part of a pr edicted Ca2+ CaM binding site of amino acids 3614-3632 [Takeshima, W., et a l, (1989) Nature 339, 439-445].