Cryo-EM structures of apo and antagonist-bound human Cav3.1

Yanyu Zhao, Gaoxingyu Huang, Qiurong Wu, Kun Wu, Ruiqi Li, Jianlin Lei, Xiaojing Pan and Nieng Yan ()
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Yanyu Zhao: Westlake University
Gaoxingyu Huang: Tsinghua University
Qiurong Wu: Tsinghua University
Kun Wu: Capital Medical University
Ruiqi Li: Capital Medical University
Jianlin Lei: Tsinghua University
Xiaojing Pan: Tsinghua University
Nieng Yan: Tsinghua University

Nature, 2019, vol. 576, issue 7787, 492-497

Abstract: Abstract Among the ten subtypes of mammalian voltage-gated calcium (Cav) channels, Cav3.1–Cav3.3 constitute the T-type, or the low-voltage-activated, subfamily, the abnormal activities of which are associated with epilepsy, psychiatric disorders and pain1–5. Here we report the cryo-electron microscopy structures of human Cav3.1 alone and in complex with a highly Cav3-selective blocker, Z9446,7, at resolutions of 3.3 Å and 3.1 Å, respectively. The arch-shaped Z944 molecule reclines in the central cavity of the pore domain, with the wide end inserting into the fenestration on the interface between repeats II and III, and the narrow end hanging above the intracellular gate like a plug. The structures provide the framework for comparative investigation of the distinct channel properties of different Cav subfamilies.

Date: 2019
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DOI: 10.1038/s41586-019-1801-3

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