Cp. Moore et al., Apocalmodulin and Ca2+ calmodulin bind to the same region on the skeletal muscle Ca2+ release channel, BIOCHEM, 38(26), 1999, pp. 8532-8537
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].