Cryo-EM structures of apo and antagonist-bound human Ca3.1.

TitleCryo-EM structures of apo and antagonist-bound human Ca3.1.
Publication TypeJournal Article
Year of Publication2019
AuthorsZhao, Y, Huang, G, Wu, Q, Wu, K, Li, R, Lei, J, Pan, X, Yan, N
JournalNature
Volume576
Issue7787
Pagination492-497
Date Published2019 12
ISSN1476-4687
KeywordsAllosteric Regulation, Amino Acid Motifs, Amino Acid Sequence, Apoproteins, Binding Sites, Calcium Channel Blockers, Calcium Channels, T-Type, Cryoelectron Microscopy, Humans, Models, Molecular, Piperidines, Protein Binding, Protein Conformation, Sequence Deletion
Abstract

<p>Among the ten subtypes of mammalian voltage-gated calcium (Ca) channels, Ca3.1-Ca3.3 constitute the T-type, or the low-voltage-activated, subfamily, the abnormal activities of which are associated with epilepsy, psychiatric disorders and pain. Here we report the cryo-electron microscopy structures of human Ca3.1 alone and in complex with a highly Ca3-selective blocker, Z944, 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 Ca subfamilies.</p>

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