Cryo-EM structures of apo and antagonist-bound human Cav3.1
Cryo-EM structures of apo and antagonist-bound human Cav3.1
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DOI：
10.1038/s41586-019-1801-3
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发表时间：
2019-12-19
期刊：
影响因子：
64.8
通讯作者：
Yan, Nieng
中科院分区：
文献类型：
--
作者：
Zhao, Yanyu;Huang, Gaoxingyu;Yan, Nieng
在哺乳动物电压门控钙（Ca-v）通道的十种亚型中，Ca（v）3.1-Ca（v）3.3构成T型或低电压激活的亚家族，其异常活动与癫痫、精神障碍和疼痛相关1 -5。在这里，我们报告的冷冻电子显微镜结构的人Ca（v）3.1单独和复杂的高度Ca（v）3-选择性阻断剂，Z9446，7，在3.3 A和3.1 A的分辨率，分别。拱形Z944分子斜倚在孔结构域的中心空腔中，宽端插入重复序列II和III之间界面上的开窗中，窄端像塞子一样悬挂在细胞内门上方。的结构提供了不同的Ca-V亚家族的不同通道特性的比较研究的框架。
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.