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
Naturejournal_title
Natureauthors
Zhao Y,Huang G,Wu Q,Wu K,Li R,Lei J,Pan X,Yan Ndoi
10.1038/s41586-019-1801-3subject
Has Abstractpub_date
2019-12-01 00:00:00pages
492-497issue
7787eissn
0028-0836issn
1476-4687pii
10.1038/s41586-019-1801-3journal_volume
576pub_type
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