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

Citation
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
Citations number
35
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMISTRY
ISSN journal
00062960 → ACNP
Volume
38
Issue
26
Year of publication
1999
Pages
8532 - 8537
Database
ISI
SICI code
0006-2960(19990629)38:26<8532:AACCBT>2.0.ZU;2-8
Abstract
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].