Alterations in calmodulin-cardiac ryanodine receptor molecular recognition in congenital arrhythmias.

ABSTRACT: Calmodulin (CaM), a ubiquitous and highly conserved Ca²⁺-sensor protein involved in the regulation of over 300 molecular targets, has been recently associated with severe forms of lethal arrhythmia. Here, we investigated how arrhythmia-associated mutations in CaM localized at the C-terminal lobe alter the molecular recognition with Ryanodine receptor 2 (RyR2), specifically expressed in cardiomyocytes. We performed an extensive structural, thermodynamic, and kinetic characterization of the variants D95V/H in the EF3 Ca²⁺-binding motif and of the D129V and D131H/E variants in the EF4 motif, and probed their interaction with RyR2. Our results show that the specific structural changes observed for individual CaM variants do not extend to the complex with the RyR2 target.

SUBMITTER: Dal Cortivo G 

PROVIDER: S-EPMC8825638 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature