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
Date Published2019 Dec
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

<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>

Alternate JournalNature
PubMed ID31766050
PubMed Central ID18083096