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DOI | 10.1038/s41586-019-1202-7 |
Cryo-EM reveals two distinct serotonin-bound conformations of full-length 5-HT3A receptor | |
Basak, Sandip1; Gicheru, Yvonne1; Rao, Shanlin2; Sansom, Mark S. P.2; Chakrapani, Sudha1,3 | |
2019-05-22 | |
发表期刊 | NATURE |
ISSN | 0028-0836 |
EISSN | 1476-4687 |
出版年 | 2018 |
卷号 | 563期号:7730页码:270-+ |
文章类型 | Article |
语种 | 英语 |
国家 | USA; England |
英文摘要 | The 5-HT3A serotonin receptor(1), a cationic pentameric ligand-gated ion channel (pLGIC), is the clinical target for management of nausea and vomiting associated with radiation and chemotherapies(2). Upon binding, serotonin induces a global conformational change that encompasses the ligand-binding extracellular domain (ECD), the transmembrane domain (TMD) and the intracellular domain (ICD), the molecular details of which are unclear. Here we present two serotonin-bound structures of the full-length 5-HT3A receptor in distinct conformations at 3.32 angstrom and 3.89 angstrom resolution that reveal the mechanism underlying channel activation. In comparison to the apo 5-HT3A receptor, serotonin-bound states underwent a large twisting motion in the ECD and TMD, leading to the opening of a 165 angstrom permeation pathway. Notably, this motion results in the creation of lateral portals for ion permeation at the interface of the TMD and ICD. Combined with molecular dynamics simulations, these structures provide novel insights into conformational coupling across domains and functional modulation. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000449943600048 |
WOS关键词 | NICOTINIC ACETYLCHOLINE-RECEPTOR ; SINGLE-CHANNEL CONDUCTANCE ; X-RAY-STRUCTURE ; 5-HYDROXYTRYPTAMINE TYPE-3 ; LIGAND RECOGNITION ; DESENSITIZATION ; LOOP ; PORE ; MECHANISM ; DOMAIN |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/203059 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Case Western Reserve Univ, Dept Physiol & Biophys, Cleveland, OH 44106 USA; 2.Univ Oxford, Dept Biochem, Oxford, England; 3.Case Western Reserve Univ, Sch Med, Dept Neurosci, Cleveland, OH 44106 USA |
推荐引用方式 GB/T 7714 | Basak, Sandip,Gicheru, Yvonne,Rao, Shanlin,et al. Cryo-EM reveals two distinct serotonin-bound conformations of full-length 5-HT3A receptor[J]. NATURE,2019,563(7730):270-+. |
APA | Basak, Sandip,Gicheru, Yvonne,Rao, Shanlin,Sansom, Mark S. P.,&Chakrapani, Sudha.(2019).Cryo-EM reveals two distinct serotonin-bound conformations of full-length 5-HT3A receptor.NATURE,563(7730),270-+. |
MLA | Basak, Sandip,et al."Cryo-EM reveals two distinct serotonin-bound conformations of full-length 5-HT3A receptor".NATURE 563.7730(2019):270-+. |
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