Journal
NATURE
Volume 576, Issue 7787, Pages 492-+Publisher
NATURE RESEARCH
DOI: 10.1038/s41586-019-1801-3
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Funding
- National Natural Science Foundation of China [81920108015, 31800628, 31621092]
- National Key R&D Program from Ministry of Science and Technology of China [2016YFA0500402, 2016YFA0501100]
- Shirley M. Tilghman endowed professorship from Princeton University
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Among the ten subtypes of mammalian voltage-gated calcium (Ca-v) channels, Ca(v)3.1-Ca(v)3.3 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 Ca(v)3.1 alone and in complex with a highly Ca(v)3-selective blocker, Z9446,7, at resolutions of 3.3 A and 3.1 A, 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-v subfamilies.
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