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

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.

journal_name

Nature

journal_title

Nature

authors

Zhao Y,Huang G,Wu Q,Wu K,Li R,Lei J,Pan X,Yan N

doi

10.1038/s41586-019-1801-3

subject

Has Abstract

pub_date

2019-12-01 00:00:00

pages

492-497

issue

7787

eissn

0028-0836

issn

1476-4687

pii

10.1038/s41586-019-1801-3

journal_volume

576

pub_type

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