Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser
2015-07-30
发表期刊NATURE
ISSN0028-0836
卷号523期号:7562页码:561-+
发表状态已发表
DOI10.1038/nature14656
摘要G-protein-coupled receptors (GPCRs) signal primarily through G proteins or arrestins. Arrestin binding to GPCRs blocks G protein interaction and redirects signalling to numerous G-protein-independent pathways. Here we report the crystal structure of a constitutively active form of human rhodopsin bound to a pre-activated form of the mouse visual arrestin, determined by serial femtosecond X-ray laser crystallography. Together with extensive biochemical and mutagenesis data, the structure reveals an overall architecture of the rhodopsin-arrestin assembly in which rhodopsin uses distinct structural elements, including transmembrane helix 7 and helix 8, to recruit arrestin. Correspondingly, arrestin adopts the pre-activated conformation, with a similar to 20 degrees rotation between the amino and carboxy domains, which opens up a cleft in arrestin to accommodate a short helix formed by the second intracellular loop of rhodopsin. This structure provides a basis for understanding GPCR-mediated arrestin-biased signalling and demonstrates the power of X-ray lasers for advancing the frontiers of structural biology.
收录类别SCI
语种英语
资助项目National Institute of General Medical Sciences PSI: Biology grants[U54 GM094618] ; National Institute of General Medical Sciences PSI: Biology grants[GM108635] ; National Institute of General Medical Sciences PSI: Biology grants[U54 GM094599] ; National Institute of General Medical Sciences PSI: Biology grants[GM097463] ; National Institute of General Medical Sciences PSI: Biology grants[U54 GM094586]
WOS研究方向Science & Technology - Other Topics
WOS类目Multidisciplinary Sciences
WOS记录号WOS:000358655200038
出版者NATURE PUBLISHING GROUP
WOS关键词PROTEIN-COUPLED RECEPTOR ; LIPIDIC CUBIC PHASE ; ROD OUTER SEGMENTS ; VISUAL ARRESTIN ; SEROTONIN RECEPTORS ; THERMAL-STABILITY ; MEMBRANE-PROTEINS ; SPACE-GROUP ; ACTIVATION ; BINDING
原始文献类型Article
引用统计
文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/2171
专题iHuman研究所
iHuman研究所_特聘教授组_Raymond Stevens组
通讯作者Xu, H. Eric
作者单位
1.Van Andel Res Inst, Ctr Struct Biol & Drug Discovery, Lab Struct Sci, Grand Rapids, MI 49503 USA
2.Arizona State Univ, Dept Chem & Biochem, Biodesign Inst, Tempe, AZ 85287 USA
3.Arizona State Univ, Ctr Appl Struct Discovery, Biodesign Inst, Tempe, AZ 85287 USA
4.Univ So Calif, Bridge Inst, Dept Chem, Los Angeles, CA 90089 USA
5.Deutsch Elektronen Synchrotron DESY, Ctr Free Elect Laser Sci, D-22607 Hamburg, Germany
6.SLAC Natl Accelerator Lab, Stanford Synchrotron Radiat Lightsource, Joint Ctr Struct Genom, Menlo Pk, CA 94025 USA
7.Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Obstet & Gynecol, Singapore 117595, Singapore
8.New York Struct Biol Ctr, Natl Resource Automated Mol Microscopy, New York, NY 10027 USA
9.Scripps Florida, Scripps Res Inst, Dept Mol Therapeut, Jupiter, FL 33458 USA
10.Univ Calif Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90095 USA
11.Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA
12.Univ Toronto, Dept Biochem, Toronto, ON M5S 1A8, Canada
13.Vanderbilt Univ, Dept Pharmacol, Nashville, TN 37232 USA
14.SLAC Natl Accelerator Lab, LCLS, Menlo Pk, CA 94025 USA
15.NSF Sci & Technol Ctr, BioXFEL, Buffalo, NY 14203 USA
16.Arizona State Univ, Dept Phys, Tempe, AZ 85287 USA
17.Beijing Computat Sci Res Ctr, Beijing 10084, Peoples R China
18.Univ Wisconsin, Dept Phys, Milwaukee, WI 53211 USA
19.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
20.Paul Scherrer Inst, Swiss Light Source, CH-5232 Villigen, Switzerland
21.Univ So Calif, Bridge Inst, Dept Biol Sci, Los Angeles, CA 90089 USA
22.Univ Dublin Trinity Coll, Sch Med & Sch Biochem & Immunol, Dublin 2, Ireland
23.Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USA
24.Paul Scherrer Inst, Lab Biomol Res, CH-5232 Villigen, Switzerland
25.Univ Konstanz, Dept Biol, D-78457 Constance, Germany
26.Chinese Acad Sci, Beijing Synchrotron Radiat Facil, Beijing 100049, Peoples R China
27.Ctr Ultrafast Imaging, D-22761 Hamburg, Germany
28.Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada
29.ShanghaiTech Univ, iHuman Inst, Shanghai 201210, Peoples R China
30.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, VARI SIMM Ctr,Ctr Struct & Funct Drug Targets, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714
Kang, Yanyong,Zhou, X. Edward,Gao, Xiang,et al. Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser[J]. NATURE,2015,523(7562):561-+.
APA Kang, Yanyong.,Zhou, X. Edward.,Gao, Xiang.,He, Yuanzheng.,Liu, Wei.,...&Xu, H. Eric.(2015).Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser.NATURE,523(7562),561-+.
MLA Kang, Yanyong,et al."Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser".NATURE 523.7562(2015):561-+.
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