The molecular basis of the inhibition of Ca_V1 calcium-dependent inactivation by the distal carboxy tail.

ABSTRACT: Ca²⁺/calmodulin-dependent inactivation (CDI) of Ca_V channels is a critical regulatory process that tunes the kinetics of Ca²⁺ entry for different cell types and physiologic responses. CDI is mediated by calmodulin (CaM), which is bound to the IQ domain of the Ca_V carboxy tail. This modulatory process is tailored by alternative splicing such that select splice variants of Ca_V1.3 and Ca_V1.4 contain a long distal carboxy tail (DCT). The DCT harbors an inhibitor of CDI (ICDI) module that competitively displaces CaM from the IQ domain, thereby diminishing CDI. While this overall mechanism is now well described, the detailed interactions required for ICDI binding to the IQ domain are yet to be elucidated. Here, we perform alanine-

SUBMITTER: Sang L 

PROVIDER: S-EPMC8054141 | biostudies-literature | 2021 Jan-Jun

REPOSITORIES: biostudies-literature