Structure-based mechanism of RyR channel operation by calcium and magnesium ions.

ABSTRACT: Ryanodine receptors (RyRs) serve for excitation-contraction coupling in skeletal and cardiac muscle cells in a noticeably different way, not fully understood at the molecular level. We addressed the structure of skeletal (RyR1) and cardiac (RyR2) isoforms relevant to gating by Ca2+ and Mg2+ ions (M2+). Bioinformatics analysis of RyR structures ascertained the EF-hand loops as the M2+ binding inhibition site and revealed its allosteric coupling to the channel gate. The intra-monomeric inactivation pathway interacts with the Ca2+-activation pathway in both RyR isoforms, and the inter-monomeric pathway, stronger in RyR1, couples to the gate through the S23*-loop of the neighbor monomer. These structural findings were implemented in the model of RyR operation based on statistical mechanics and

SUBMITTER: Zahradnikova A 

PROVIDER: S-EPMC12119028 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature