Kinetics insight into the roles of the N- and C-lobes of calmodulin in RyR1 channel regulation.

ABSTRACT: Calmodulin (CaM) activates the skeletal muscle Ca²⁺ release channel (ryanodine receptor, RyR1) at nanomolar Ca²⁺ and inhibits it at micromolar Ca²⁺. CaM conversion from RyR1 activator to inhibitor is due to structural changes induced by Ca²⁺ binding at CaM's two lobes. However, it remains unclear which lobe provides the switch for this conversion. Here, we attached the environment-sensitive fluorophore acrylodan (Acr) at either lobe of intact CaM or lobe-specific Ca²⁺-sensitive CaM mutants, and monitored the effects of Ca²⁺ binding via the fluorescence change of free or RyR1-bound ^AcrCaM. Using steady state measurements, we found that Ca²⁺ binding to free CaM causes a dramatic structural change in the N

SUBMITTER: Zhang J 

PROVIDER: S-EPMC11923823 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature