Structures of the R-type human Ca_v2.3 channel reveal conformational crosstalk of the intracellular segments.

ABSTRACT: The R-type voltage-gated Ca²⁺ (Ca_v) channels Ca_v2.3, widely expressed in neuronal and neuroendocrine cells, represent potential drug targets for pain, seizures, epilepsy, and Parkinson's disease. Despite their physiological importance, there have lacked selective small-molecule inhibitors targeting these channels. High-resolution structures may aid rational drug design. Here, we report the cryo-EM structure of human Ca_v2.3 in complex with α2δ-1 and β3 subunits at an overall resolution of 3.1 Å. The structure is nearly identical to that of Ca_v2.2, with VSD_II in the down state and the other three VSDs up. A phosphatidylinositol 4,5-bisphosphate (PIP2) molecule binds to the interface of VSD_II and the tightly closed p

SUBMITTER: Yao X 

PROVIDER: S-EPMC9708679 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature