The central domain of cardiac ryanodine receptor governs channel activation, regulation, and stability.

ABSTRACT: Structural analyses identified the central domain of ryanodine receptor (RyR) as a transducer converting conformational changes in the cytoplasmic platform to the RyR gate. The central domain is also a regulatory hub encompassing the Ca²⁺-, ATP-, and caffeine-binding sites. However, the role of the central domain in RyR activation and regulation has yet to be defined. Here, we mutated five residues that form the Ca²⁺ activation site and 10 residues with negatively charged or oxygen-containing side chains near the Ca²⁺ activation site. We also generated eight disease-associated mutations within the central domain of RyR2. We determined the effect of these mutations on Ca²⁺, ATP, and caffeine activation and Mg²⁺ inhibition of RyR2. Mutat

SUBMITTER: Guo W 

PROVIDER: S-EPMC7667974 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature