Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser

被引：578

作者：

Kang, Yanyong ^{[1
]}

Zhou, X. Edward ^{[1
]}

Gao, Xiang ^{[1
]}

He, Yuanzheng ^{[1
]}

Liu, Wei ^{[2
,3
]}

Ishchenko, Andrii ^{[4
]}

Barty, Anton ^{[5
]}

Sathish, D. ^{[5
]}

Yefanov, Oleksandr ^{[5
]}

Han, Gye Won ^{[4
]}

Xu, Qingping ^{[6
]}

de Waal, Parker W. ^{[1
]}

Ke, Jiyuan ^{[1
]}

Tan, M. H. Eileen ^{[1
,7
]}

Zhang, Chenghai ^{[1
]}

Moeller, Arne ^{[8
]}

West, Graham M. ^{[9
]}

Pascal, Bruce D. ^{[9
]}

Van Eps, Ned ^{[10
,11
]}

Caro, Lydia N. ^{[12
]}

Vishnivetskiy, Sergey A. ^{[13
]}

Lee, Regina J. ^{[13
]}

Suino-Powell, Kelly M. ^{[13
]}

Gu, Xin ^{[1
]}

Pal, Kuntal ^{[1
]}

Ma, Jinming ^{[1
]}

Zhi, Xiaoyong ^{[1
]}

Boutet, Sebastien ^{[14
]}

Williams, Garth J. ^{[14
]}

Messerschmidt, Marc ^{[14
,15
]}

Gati, Cornelius ^{[5
]}

Zatsepin, Nadia A. ^{[2
,3
,16
]}

Wang, Dingjie ^{[2
,3
,16
]}

James, Daniel ^{[2
,3
,16
]}

Basu, Shibom ^{[2
,3
,16
]}

Roy-Chowdhury, Shatabdi ^{[2
,3
,16
]}

Conrad, Chelsie E. ^{[2
,3
]}

Coe, Jesse ^{[2
,3
]}

Liu, Haiguang ^{[2
,3
,17
]}

Lisova, Stella ^{[2
,3
]}

Kupitz, Christopher ^{[2
,3
,18
]}

Grotjohann, Ingo ^{[2
,3
]}

Fromme, Raimund ^{[2
,3
]}

Jiang, Yi ^{[19
]}

Tan, Minjia ^{[19
]}

Yang, Huaiyu ^{[19
]}

Li, Jun ^{[7
]}

Wang, Meitian ^{[20
]}

Zheng, Zhong ^{[21
]}

Li, Dianfan ^{[22
]}

机构：

[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

来源：

NATURE | 2015年 / 523卷 / 7562期

基金：

爱尔兰科学基金会; 瑞士国家科学基金会; 美国国家卫生研究院;

关键词：

LIPIDIC CUBIC PHASE; VISUAL ARRESTIN; SPACE-GROUP; PROTEIN; ACTIVATION; BINDING; EXPRESSION; MICROSCOPY; PIGGYBAC; SYSTEM;

D O I：

10.1038/nature14656

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

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.

引用

页码：561 / +

页数：31

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