RyR2 disease mutations at the C-terminal domain intersubunit interface alter closed-state stability and channel activation.

ABSTRACT: Ryanodine receptors (RyRs) are ion channels that mediate the release of Ca²⁺ from the sarcoplasmic reticulum/endoplasmic reticulum, mutations of which are implicated in a number of human diseases. The adjacent C-terminal domains (CTDs) of cardiac RyR (RyR2) interact with each other to form a ring-like tetrameric structure with the intersubunit interface undergoing dynamic changes during channel gating. This mobile CTD intersubunit interface harbors many disease-associated mutations. However, the mechanisms of action of these mutations and the role of CTD in channel function are not well understood. Here, we assessed the impact of CTD disease-associated mutations P4902S, P4902L, E4950K, and G4955E on Ca²⁺- and caffeine-mediated activation of RyR2. The G4955E mutation d

SUBMITTER: Guo W 

PROVIDER: S-EPMC8214192 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature