The Crystal Structure of Calmodulin Bound to the Cardiac Ryanodine Receptor (RyR2) at Residues Phe4246-Val4271 Reveals a Fifth Calcium Binding Site.

ABSTRACT: Calmodulin (CaM) regulates the activity of a Ca²⁺ channel known as the cardiac ryanodine receptor (RyR2), which facilitates the release of Ca²⁺ from the sarcoplasmic reticulum during excitation-contraction coupling in cardiomyocytes. Mutations that disrupt this CaM-dependent channel inactivation result in cardiac arrhythmias. RyR2 contains three different CaM binding sites: CaMBD1 (residues 1940-1965), CaMBD2 (residues 3580-3611), and CaMBD3 (residues 4246-4275). Here, we report a crystal structure of Ca²⁺-bound CaM bound to RyR2 CaMBD3. The structure reveals Ca²⁺ bound to the four EF-hands of CaM as well as a fifth Ca²⁺ bound to CaM in the interdomain linker region involving Asp81 and Glu85. The CaM mutant E85A abolishes the binding o

SUBMITTER: Yu Q 

PROVIDER: S-EPMC8211408 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature