The voltage-gated calcium channel Cav1.1 is engaged in the excitation-contraction coupling of skeletal muscles. The Cav1.1 complex consists of the pore-forming subunit α1 and auxiliary subunits α2δ, β, and γ. We report the structure of the rabbit Cav1.1 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 (VSDIV), whereas the cytosolic β subunit is located adjacent to VSDII 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 Cav channel and provides a framework for understanding the function and disease mechanisms of Cav and Nav channels.
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