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

TitleCryo-EM structures of apo and antagonist-bound human Cav3.1.
Publication TypeJournal Article
Year of Publication2019
AuthorsZhao, Y, Huang, G, Wu, Q, Wu, K, Li, R, Lei, J, Pan, X, Yan, N
JournalNature
Date Published2019 Nov 25
ISSN1476-4687
Abstract

Among the 10 subtypes of mammalian voltage-gated calcium (Cav) channels (VGCC), Cav3.1-3.3 constitute the T-type, or the low voltage-activated, subfamily, whose abnormal activities are associated with epilepsy, psychiatric disorders, and pain1-5. Here we report the cryo-EM 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 between different Cav subfamilies.

DOI10.1038/s41586-019-1801-3
Alternate JournalNature
PubMed ID31766050