A three-way inter-molecular network accounts for the Ca_Vα2δ1-induced functional modulation of the pore-forming Ca_V1.2 subunit.

ABSTRACT: L-type Ca_V1.2 channels are essential for the excitation-contraction coupling in cardiomyocytes and are hetero-oligomers of a pore-forming Ca_Vα1C assembled with Ca_Vβ and Ca_Vα2δ1 subunits. A direct interaction between Ca_Vα2δ1 and Asp-181 in the first extracellular loop of Ca_Vα1 reproduces the native properties of the channel. A 3D model of the von Willebrand factor type A (VWA) domain of Ca_Vα2δ1 complexed with the voltage sensor domain of Ca_Vα1C suggests that Ser-261 and Ser-263 residues in the metal ion-dependent adhesion site (MIDAS) motif are determinant in this interaction, but this hypothesis is untested. Here, coimmunoprecipitation assays and patch-clamp experiments of single-substitution variants r

SUBMITTER: Briot J 

PROVIDER: S-EPMC5950009 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature