Apocalmodulin and Ca2+ Calmodulin Bind to the Same Region on the Skeletal Muscle Ca2+ Release Channel

• Published in: Biochemistry (Easton) 1999-06, Vol.38 (26), p.8532-8537
• Main Authors: Moore, Catherine Porter, Rodney, George, Zhang, Jia-Zheng, Santacruz-Toloza, Lucia, Strasburg, Gale, Hamilton, Susan L
• Format: Article
• Language: English
• Subjects: Animals; Apoproteins - chemistry; Apoproteins - metabolism; Binding Sites; Calcium - metabolism; Calmodulin - chemistry; Calmodulin - metabolism; Hydrolysis; Life Sciences (General); Muscle, Skeletal - chemistry; Muscle, Skeletal - metabolism; Peptide Fragments - chemistry; Peptide Fragments - metabolism; Ryanodine Receptor Calcium Release Channel - chemistry; Ryanodine Receptor Calcium Release Channel - metabolism; Space life sciences; Sulfur Radioisotopes; Trypsin - metabolism
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi9907431

The skeletal muscle Ca2+ release channel (RYR1) is regulated by calmodulin in both its Ca2+-free (apocalmodulin) and Ca2+-bound (Ca2+ calmodulin) states. Apocalmodulin is an activator of the channel, and Ca2+ calmodulin is an inhibitor of the channel. Both apocalmodulin and Ca2+ calmodulin binding sites on RYR1 are destroyed by a mild tryptic digestion of the sarcoplasmic reticulum membranes, but calmodulin (either form), bound to RYR1 prior to tryptic digestion, protects both the apocalmodulin and Ca2+ calmodulin sites from tryptic destruction. The protected sites are after arginines 3630 and 3637 on RYR1. These studies suggest that both Ca2+ calmodulin and apocalmodulin bind to the same or overlapping regions on RYR1 and block access of trypsin to sites at amino acids 3630 and 3637. This sequence is part of a predicted Ca2+ CaM binding site of amino acids 3614−3642 [Takeshima, H., et al. (1989) Nature 339, 439−445].