小柯机器人

清华大学、美国普林斯顿大学颜宁团队解析了apo和拮抗剂结合的人源Ca_v3.1冷冻电镜结构。相关论文于2019年11月25日在线发表于国际学术期刊《自然》。

颜宁团队报告了单独的人类Ca_v3.1以及与其高选择性阻滞剂Z944结合的冷冻电镜结构，其分辨率分别为3.3Å和3.1Å。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之间的界面的窗孔中，窄端像塞子一样悬在细胞内通道上方。

这些结构为比较性研究不同Ca_v亚家族之间不同的通道特性提供了框架。

据介绍，在哺乳动物的电压门控钙（Ca_v）通道（VGCC）的10个亚型中，Ca_v3.1–3.3构成T型或低电压激活的亚家族，其异常活动与癫痫、精神病和疼痛相关。

附：英文原文

Title: Cryo-EM structures of apo and antagonist-bound human Ca v 3.1

Author: Yanyu Zhao, Gaoxingyu Huang, Qiurong Wu, Kun Wu, Ruiqi Li, Jianlin Lei, Xiaojing Pan, Nieng Yan

Issue&Volume: 2019-11-25

Abstract: 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 and 3.1 , 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.

DOI: 10.1038/s41586-019-1801-3

Source: https://www.nature.com/articles/s41586-019-1801-3

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html