GSTDTAP  > 地球科学
DOI10.1038/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
ISSN0028-0836
EISSN1476-4687
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
被引频次:72[WOS]   [WOS记录]     [WOS相关记录]
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-+.
条目包含的文件
条目无相关文件。
个性服务
推荐该条目
保存到收藏夹
查看访问统计
导出为Endnote文件
谷歌学术
谷歌学术中相似的文章
[Basak, Sandip]的文章
[Gicheru, Yvonne]的文章
[Rao, Shanlin]的文章
百度学术
百度学术中相似的文章
[Basak, Sandip]的文章
[Gicheru, Yvonne]的文章
[Rao, Shanlin]的文章
必应学术
必应学术中相似的文章
[Basak, Sandip]的文章
[Gicheru, Yvonne]的文章
[Rao, Shanlin]的文章
相关权益政策
暂无数据
收藏/分享
所有评论 (0)
暂无评论
 

除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。