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

Zhao Y, Huang G, Wu Q, Wu K, Li R, Lei J, Pan X, Yan N
Nature 576 492-497 (2019)
Cited: 72 times
EuropePMC logo PMID: 31766050

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.

Reviews - 6kzo mentioned but not cited (2)

  1. P-Loop Channels: Experimental Structures, and Physics-Based and Neural Networks-Based Models. Tikhonov DB, Zhorov BS. Membranes (Basel) 12 229 (2022)
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Articles - 6kzo mentioned but not cited (12)

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  4. A rare CACNA1H variant associated with amyotrophic lateral sclerosis causes complete loss of Cav3.2 T-type channel activity. Stringer RN, Jurkovicova-Tarabova B, Huang S, Haji-Ghassemi O, Idoux R, Liashenko A, Souza IA, Rzhepetskyy Y, Lacinova L, Van Petegem F, Zamponi GW, Pamphlett R, Weiss N. Mol Brain 13 33 (2020)
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