Ca²⁺-dependent calmodulin binding to cardiac ryanodine receptor (RyR2) calmodulin-binding domains.

ABSTRACT: The Ca²⁺ sensor calmodulin (CaM) regulates cardiac ryanodine receptor (RyR2)-mediated Ca²⁺ release from the sarcoplasmic reticulum. CaM inhibits RyR2 in a Ca²⁺-dependent manner and aberrant CaM-dependent inhibition results in life-threatening cardiac arrhythmias. However, the molecular details of the CaM-RyR2 interaction remain unclear. Four CaM-binding domains (CaMBD1a, -1b, -2, and -3) in RyR2 have been proposed. Here, we investigated the Ca²⁺-dependent interactions between CaM and these CaMBDs by monitoring changes in the fluorescence anisotropy of carboxytetramethylrhodamine (TAMRA)-labeled CaMBD peptides during titration with CaM at a wide range of Ca²⁺ concentrations. We showed that CaM bound to all four CaMBDs with affinities th

SUBMITTER: Brohus M 

PROVIDER: S-EPMC6340113 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature