Structural and functional interactions between the EF hand domain and S2-S3 loop in the type-1 ryanodine receptor ion channel.

ABSTRACT: Previous cryo-electron micrographs suggested that the skeletal muscle Ca²⁺ release channel, ryanodine receptor (RyR)1, is regulated by intricate interactions between the EF hand Ca²⁺ binding domain and the cytosolic loop (S2-S3 loop). However, the precise molecular details of these interactions and functional consequences of the interactions remain elusive. Here, we used molecular dynamics simulations to explore the specific amino acid pairs involved in hydrogen bond interactions within the EF hand-S2-S3 loop interface. Our simulations unveiled two key interactions: (1) K4101 (EF hand) with D4730 (S2-S3 loop) and (2) E4075, Q4078, and D4079 (EF hand) with R4736 (S2-S3 loop). To probe the functional significance of these interactions, we constructed mutant RyR1 complem

SUBMITTER: Chirasani VR 

PROVIDER: S-EPMC10832476 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature