| 题名 | Cryo-EM structure of human heptameric pannexin 2 channel |
| 作者 | |
| 通讯作者 | Wang，Daping |
| 发表日期 | 2023-03-03
|
| DOI | |
| 发表期刊 | |
| EISSN | 2041-1723
|
| 卷号 | 14期号:1 |
| 摘要 | Pannexin 2 (Panx2) is a large-pore ATP-permeable channel with critical roles in various physiological processes, such as the inflammatory response, energy production and apoptosis. Its dysfunction is related to numerous pathological conditions including ischemic brain injury, glioma and glioblastoma multiforme. However, the working mechanism of Panx2 remains unclear. Here, we present the cryo-electron microscopy structure of human Panx2 at a resolution of 3.4 Å. Panx2 structure assembles as a heptamer, forming an exceptionally wide channel pore across the transmembrane and intracellular domains, which is compatible with ATP permeation. Comparing Panx2 with Panx1 structures in different states reveals that the Panx2 structure corresponds to an open channel state. A ring of seven arginine residues located at the extracellular entrance forms the narrowest site of the channel, which serves as the critical molecular filter controlling the permeation of substrate molecules. This is further verified by molecular dynamics simulations and ATP release assays. Our studies reveal the architecture of the Panx2 channel and provide insights into the molecular mechanism of its channel gating. |
| 相关链接 | [Scopus记录] |
| 收录类别 | |
| 语种 | 英语
|
| 重要成果 | NI论文
|
| 学校署名 | 第一
; 通讯
|
| 资助项目 | National Natural Science Foundation of China["31900046","81972085","82172465","32271251","82201315","32161133022"]
; Shenzhen Science and Technology Program["JCYJ20220530115214033","JCYJ20200109114818703"]
; National Science and Technology Innovation 2030 Major Program[2022ZD0211900]
; Science and Technology Innovation Committee of Shenzhen[JCYJ20200109150700942]
; Key-Area Research and Development Program of Guangdong Province[2019B030335001]
; Shenzhen Fund for Guangdong Provincial High Level Clinical Key Specialties[SZGSP013]
; Shenzhen Key Medical Discipline Construction Fund[SZXK042]
; Guangdong Provincial Key Laboratory of Advanced Biomaterials[2022B1212010003]
; Shenzhen Key Laboratory of Computer Aided Drug Discovery, Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China[ZDSYS20201230165400001]
; Chinese Academy of Science President's International Fellowship Initiative (PIFI)[2020FSB0003]
; NSFC-SNSF Funding[32161133022]
|
| WOS研究方向 | Science & Technology - Other Topics
|
| WOS类目 | Multidisciplinary Sciences
|
| WOS记录号 | WOS:001066713800015
|
| 出版者 | |
| Scopus记录号 | 2-s2.0-85149795103
|
| 来源库 | Scopus
|
| 引用统计 |
被引频次[WOS]：7
|
| 成果类型 | 期刊论文 |
| 条目标识符 | http://sustech.caswiz.com/handle/2SGJ60CL/513348 |
| 专题 | 工学院_生物医学工程系 生命科学学院 |
| 作者单位 | 1.Department of Biomedical Engineering,Southern University of Science and Technology,Shenzhen,518055,China 2.Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences,Shenzhen,518055,China 3.Department of Child and Adolescent Psychiatry,Shenzhen Kangning Hospital,Shenzhen Mental Health Center,Shenzhen,518020,China 4.School of Life Sciences,Southern University of Science and Technology,Shenzhen,518055,China 5.Interdisciplinary Center for Brain Information,The Brain Cognition and Brain Disease Institute,Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences,Shenzhen,Guangdong,518055,China 6.Faculty of Life and Health Sciences,Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences,Shenzhen,Guangdong,518055,China 7.Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions,Shenzhen,Guangdong,518055,China 8.Department of Orthopedics,Shenzhen Intelligent Orthopaedics and Biomedical Innovation Platform,Guangdong Provincial Research Center for Artificial Intelligence and Digital Orthopedic Technology,Shenzhen Second People’s Hospital,The First Affiliated Hospital of Shenzhen University,Shenzhen,518000,China 9.Guangdong Provincial Key Laboratory of Advanced Biomaterials,Southern University of Science and Technology,Shenzhen,518055,China |
| 第一作者单位 | 生物医学工程系 |
| 通讯作者单位 | 生物医学工程系 |
| 第一作者的第一单位 | 生物医学工程系 |
| 推荐引用方式 GB/T 7714 |
Zhang，Hang,Wang，Shiyu,Zhang，Zhenzhen,et al. Cryo-EM structure of human heptameric pannexin 2 channel[J]. Nature Communications,2023,14(1).
|
| APA |
Zhang，Hang.,Wang，Shiyu.,Zhang，Zhenzhen.,Hou，Mengzhuo.,Du，Chunyu.,...&Zhang，Huawei.(2023).Cryo-EM structure of human heptameric pannexin 2 channel.Nature Communications,14(1).
|
| MLA |
Zhang，Hang,et al."Cryo-EM structure of human heptameric pannexin 2 channel".Nature Communications 14.1(2023).
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| 条目包含的文件 | ||||||
| 文件名称/大小 | 文献类型 | 版本类型 | 开放类型 | 使用许可 | 操作 | |
| Cryo-EM structure of（3121KB） | -- | -- | 开放获取 | -- | 浏览 | |
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