Cryo-EM structures of apo and antagonist-bound human Ca_v3.1

Zhao Yanyu; Huang Gaoxingyu; Wu Qiurong; Wu Kun; Li Ruiqi; Lei Jianlin; Pan Xiaojing; Yan Nieng

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Cryo-EM structures of apo and antagonist-bound human Ca_v3.1

机译：载脂蛋白和结合拮抗剂的人类Ca_v3.1的低温电磁结构

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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.

机译：在哺乳动物的电压门控钙（Ca-v）通道的十个亚型中，Ca（v）3.1-Ca（v）3.3构成T型或低压激活的亚家族，其异常活动是与癫痫，精神疾病和疼痛有关1-5。在这里，我们报告人类Ca（v）3.1单独和与高度Ca（v）3选择性阻滞剂Z9446,7配合使用的冷冻电子显微镜结构，其分辨率分别为3.3 A和3.1A。弓形的Z944分子在孔结构域的中心腔中倾斜，宽端插入重复序列II和III之间界面的窗孔中，而窄端则像塞子一样悬在细胞内门上方。这些结构为比较研究不同Ca-v亚家族的独特通道特性提供了框架。

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《Nature》 |2019年第7787期|492-497|共6页
作者
Zhao Yanyu; Huang Gaoxingyu; Wu Qiurong; Wu Kun; Li Ruiqi; Lei Jianlin; Pan Xiaojing; Yan Nieng;
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Westlake Univ Sch Life Sci Key Lab Struct Biol Zhejiang Prov Hangzhou Zhejiang Peoples R China|Westlake Inst Adv Study Inst Biol Hangzhou Zhejiang Peoples R China;

Tsinghua Univ Sch Life Sci Tsinghua Peking Joint Ctr Life Sci State Key Lab Membrane Biol Beijing Adv Innovat C Beijing Peoples R China;

Capital Med Univ Beijing Chao Yang Hosp Med Res Ctr Beijing Key Lab Cardiopulm Cerebral Resuscit Beijing Peoples R China;

Tsinghua Univ Sch Life Sci Technol Ctr Prot Sci Minist Educ Key Lab Prot Sci Beijing Peoples R China;

Tsinghua Univ Sch Life Sci Tsinghua Peking Joint Ctr Life Sci State Key Lab Membrane Biol Beijing Adv Innovat C Beijing Peoples R China|Princeton Univ Dept Mol Biol Princeton NJ 08544 USA;

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收录信息美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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1. Ligand discrimination and gating in cyclic nucleotide-gated ion channels from apo and partial agonist-bound cryo-EM structures [J] . Jan Rheinberger, Xiaolong Gao, Philipp AM Schmidpeter, eLife journal . 2018,第september期

机译：从载脂蛋白和部分激动剂结合的冷冻EM结构中，在环状核苷酸门控离子通道中的配体识别和门控
2. Ligand discrimination and gating in cyclic nucleotide-gated ion channels from apo and partial agonist-bound cryo-EM structures [J] . Jan Rheinberger, Xiaolong Gao, Philipp AM Schmidpeter, eLife journal . 2018,第july期

机译：从载脂蛋白和部分激动剂结合的冷冻EM结构中，在环状核苷酸门控离子通道中的配体识别和门控
3. Crystal structures of free and antagonist-bound states of human α9 nicotinic receptor extracellular domain [J] . Marios Zouridakis, Petros Giastas, Eleftherios Zarkadas, Nature structural & molecular biology . 2014,第11期

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Cryo-EM structures of apo and antagonist-bound human Ca_v3.1

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