Structure of the voltage-gated calcium channel Ca_v1.1 complex

The voltage-gated calcium channel Ca_v1.1 is engaged in the excitation-contraction coupling of skeletal muscles. The Ca_v1.1 complex consists of the pore-forming subunit α₁ and auxiliary subunits α₂δ, β, and γ. We report the structure of the rabbit Ca_v1.1 complex determined by single-particle cryo-electron microscopy. The four homologous repeats of the α₁ subunit are arranged clockwise in the extracellular view. The γ subunit, whose structure resembles claudins, interacts with the voltage-sensing domain of repeat IV (VSD_IV), whereas the cytosolic β subunit is located adjacent to VSD_II of α₁. The α₂ subunit interacts with the extracellular loops of repeats I to III through its VWA and Cache1 domains. The structure reveals the architecture of a prototypical eukaryotic Ca_v channel and provides a framework for understanding the function and disease mechanisms of Ca_v and Nav channels.