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Science. 2015 Dec 18;350(6267):aad2395. doi: 10.1126/science.aad2395.

Structure of the voltage-gated calcium channel Cav1.1 complex.

Author information

1
State Key Laboratory of Membrane Biology, Tsinghua University, Beijing 100084, China. Tsinghua-Peking Joint Center for Life Sciences, Tsinghua University, Beijing 100084, China. Center for Structural Biology, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China.
2
National Institute of Biological Sciences, Beijing 102206, China.
3
State Key Laboratory of Membrane Biology, Tsinghua University, Beijing 100084, China. Tsinghua-Peking Joint Center for Life Sciences, Tsinghua University, Beijing 100084, China. Center for Structural Biology, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China. nyan@tsinghua.edu.cn.

Abstract

The voltage-gated calcium channel Ca(v)1.1 is engaged in the excitation-contraction coupling of skeletal muscles. The Ca(v)1.1 complex consists of the pore-forming subunit α1 and auxiliary subunits α2δ, β, and γ. We report the structure of the rabbit Ca(v)1.1 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 Na(v) channels.

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PMID:
26680202
DOI:
10.1126/science.aad2395
[Indexed for MEDLINE]

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