|Title||Cryo-EM structures of apo and antagonist-bound human Cav3.1.|
|Publication Type||Journal Article|
|Year of Publication||2019|
|Authors||Zhao, Y, Huang, G, Wu, Q, Wu, K, Li, R, Lei, J, Pan, X, Yan, N|
|Date Published||2019 Nov 25|
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.