<br>多种药物和神经毒素 Calciseptine 抑制人 Cav1.2 的结构基础,Cell

当前位置： X-MOL 学术 › Cell › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

多种药物和神经毒素 Calciseptine 抑制人 Cav1.2 的结构基础
Cell ( IF 45.5 ) Pub Date : 2023-11-15 , DOI: 10.1016/j.cell.2023.10.007
Shuai Gao ₁ , Xia Yao ₁ , Jiaofeng Chen ₂ , Gaoxingyu Huang ₃ , Xiao Fan ₄ , Lingfeng Xue ₅ , Zhangqiang Li ₂ , Tong Wu ₂ , Yupeng Zheng ₆ , Jian Huang ₄ , Xueqin Jin ₂ , Yan Wang ₇ , Zhifei Wang ₇ , Yong Yu ₇ , Lei Liu ₆ , Xiaojing Pan ₈ , Chen Song ₅ , Nieng Yan ₉

Affiliation

Department of Urology, Zhongnan Hospital of Wuhan University, TaiKang Center for Life and Medical Sciences, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China; Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Beijing Frontier Research Center for Biological Structures, Tsinghua-Peking Center for Life Sciences, State Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Institute of Biology, Westlake Institute for Advanced Study, Zhejiang Provincial Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang 310024, China.
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Center for Quantitative Biology, Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.
Tsinghua-Peking Center for Life Sciences, Ministry of Education Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Center for Synthetic and Systems Biology, Department of Chemistry, Tsinghua University, Beijing 100084, China.
Department of Biological Sciences, St. John's University, Queens, NY 11439, USA.
Beijing Frontier Research Center for Biological Structures, Tsinghua-Peking Center for Life Sciences, State Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China; Shenzhen Medical Academy of Research and Translation, Shenzhen, Guangdong 518107, China.
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA; Beijing Frontier Research Center for Biological Structures, Tsinghua-Peking Center for Life Sciences, State Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China; Shenzhen Medical Academy of Research and Translation, Shenzhen, Guangdong 518107, China.

Ca1.2 通道在各种神经元和生理过程中发挥着至关重要的作用。在这里，我们展示了人 Ca1.2 的冷冻电镜结构，包括其 apo 形式以及与几种药物以及肽神经毒素 Calciseptine 的复合物。大多数结构，apo 或与卡西普汀、氨氯地平或胺碘酮和索非布韦的组合结合，表现出一致的失活构象，具有密封门、三个上电压感应域 (VSD) 和一个下 VSD。 Calciseptine 位于孔域的肩部，远离渗透路径。相比之下，当将抗痉挛药物匹维溴铵插入Na通道中IFM结合位点的空腔时，会发生一系列结构变化，包括VSD的向上运动以及选择性过滤器及其周围节段的扩张重复III。同时，S4-5 与 S5 合并成为单个螺旋，导致细胞内门变宽但仍然不导电。

"点击查看英文标题和摘要"

更新日期：2023-11-15

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南