Ligand activation mechanisms of human KCNQ2 channel
文献类型：期刊论文
| 作者 | Ma, Demin1,2; Zheng, Yueming3,4; Li, Xiaoxiao1,2; Zhou, Xiaoyu3,4; Yang, Zhenni1,2; Zhang, Yan1,2; Wang, Long3; Zhang, Wenbo3; Fang, Jiajia5; Zhao, Guohua5 |
| 刊名 | Nature communications
 |
| 出版日期 | 2023-10-19 |
| 卷号 | 14期号:1页码:6632 |
| ISSN号 | 2041-1723 |
| DOI | 10.1038/s41467-023-42416-x |
| 文献子类 | Article |
| 英文摘要 | The human voltage-gated potassium channel KCNQ2/KCNQ3 carries the neuronal M-current, which helps to stabilize the membrane potential. KCNQ2 can be activated by analgesics and antiepileptic drugs but their activation mechanisms remain unclear. Here we report cryo-electron microscopy (cryo-EM) structures of human KCNQ2-CaM in complex with three activators, namely the antiepileptic drug cannabidiol (CBD), the lipid phosphatidylinositol 4,5-bisphosphate (PIP2), and HN37 (pynegabine), an antiepileptic drug in the clinical trial, in an either closed or open conformation. The activator-bound structures, along with electrophysiology analyses, reveal the binding modes of two CBD, one PIP2, and two HN37 molecules in each KCNQ2 subunit, and elucidate their activation mechanisms on the KCNQ2 channel. These structures may guide the development of antiepileptic drugs and analgesics that target KCNQ2. |
| 语种 | 英语 |
| WOS记录号 | MEDLINE: 37857637 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/309614]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Gao, Zhaobing; Guo, Jiangtao |
| 作者单位 | 1.Department of Biophysics and Department of Neurology of the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China. 2.Nanhu Brain-computer Interface Institute, Hangzhou, 311100, China. 3.State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China. 4.University of Chinese Academy of Sciences, 19A Yuquan Road, Beijing, 100049, China. 5.Department of Neurology of the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang, 322000, China. 6.Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao SAR, China. 7.State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China. zbgao@simm.ac.cn. 8.University of Chinese Academy of Sciences, 19A Yuquan Road, Beijing, 100049, China. zbgao@simm.ac.cn. 9.Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan, 528437, China. zbgao@simm.ac.cn. 10.Department of Biophysics and Department of Neurology of the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China. jiangtaoguo@zju.edu.cn. |
| 推荐引用方式 GB/T 7714 | Ma, Demin,Zheng, Yueming,Li, Xiaoxiao,et al. Ligand activation mechanisms of human KCNQ2 channel[J]. Nature communications,2023,14(1):6632. |
| APA | Ma, Demin.,Zheng, Yueming.,Li, Xiaoxiao.,Zhou, Xiaoyu.,Yang, Zhenni.,...&Guo, Jiangtao.(2023).Ligand activation mechanisms of human KCNQ2 channel.Nature communications,14(1),6632. |
| MLA | Ma, Demin,et al."Ligand activation mechanisms of human KCNQ2 channel".Nature communications 14.1(2023):6632. |
入库方式： OAI收割
来源：上海药物研究所
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