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, Nieng Yan

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)492-497
Number of pages6
JournalNature
Volume576
Issue number7787
DOIs
StatePublished - Dec 19 2019

All Science Journal Classification (ASJC) codes

  • General

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