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Molecular assembly of rhodopsin with G protein-coupled receptor kinases

文献类型：期刊论文

作者He, Yuanzheng6; Gao, Xiang6; Goswami, Devrishi5,7; Hou, Li1; Pal, Kuntal6; Yin, Yanting1,6; Zhao, Gongpu2; Ernst, Oliver P.3,4; Griffin, Patrick7; Melcher, Karsten6
刊名CELL RESEARCH
出版日期2017-06
卷号27期号:6页码:728-747
关键词rhodopsin GPCR GRK1 GRK5 Q41L
ISSN号1001-0602
DOI10.1038/cr.2017.72
文献子类Article
英文摘要G protein-coupled receptor kinases (GRKs) play pivotal roles in desensitizing GPCR signaling but little is known about how GRKs recognize and phosphorylate GPCRs due to the technical difficulties in detecting the highly dynamic GPCR/GRK interaction. By combining a genetic approach with multiple biochemical assays, we identified the key determinants for the assembly of the prototypical GPCR rhodopsin with its kinase GRK1. Our work reveals that the regulatory G-protein signaling homology (RH) domain of GRKs is the primary binding site to GPCRs and an active conformation of the GRK1 kinase domain is required for efficient interaction with rhodopsin. In addition, we provide a mechanistic solution for the longstanding puzzle about the gain-of-function Q41L mutation in GRK5. This mutation is in the RH domain and increases the capacity of the GRK mutant to interact with and to desensitize GPCRs. Finally we present the principal architecture of a rhodopsin/GRK complex through negative stain electron microscopy reconstruction. Together, these data define the key components for the rhodopsin/GRK1 interaction and provide a framework for understanding GRK-mediated desensitization of GPCRs.
WOS关键词CRYSTAL-STRUCTURE ; DRUGGABLE GENOME ; STRUCTURAL BASIS ; PHOSPHORYLATION ; ACTIVATION ; INSIGHTS ; POLYMORPHISM ; INHIBITOR ; REGULATOR ; TERMINUS
资助项目National Institute of Health[DK071662] ; American Asthma Foundation[00000000] ; Jay and Betty Van Andel Foundation[00000000] ; Ministry of Science and Technology (China)[2012ZX09301001] ; Ministry of Science and Technology (China)[2012CB910403] ; Ministry of Science and Technology (China)[2013CB910600] ; Ministry of Science and Technology (China)[XDB08020303] ; Ministry of Science and Technology (China)[2013ZX09507001] ; Van Andel Research Institute Cryo-EM core facility[00000000] ; Canada Excellence Research Chairs program[00000000] ; Anne and Max Tanenbaum Chair in Neuroscience[00000000]
WOS研究方向Cell Biology
语种英语
CSCD记录号CSCD:6016600
WOS记录号WOS:000402545200006
出版者INST BIOCHEMISTRY & CELL BIOLOGY
源URL[http://119.78.100.183/handle/2S10ELR8/272643]  
专题药物靶标结构与功能中心
通讯作者He, Yuanzheng; Xu, H. Eric
作者单位1.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;
2.Van Andel Res Inst, Cryo EM Core, Grand Rapids, MI 49503 USA;
3.Univ Toronto, Dept Biochem, Toronto, ON M5S 1A8, Canada;
4.Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada;
5.Amgen Inc, Thousand Oaks, CA 91320 USA
6.Van Andel Res Inst, Ctr Struct Biol & Drug Discovery, Lab Struct Sci, Grand Rapids, MI 49503 USA;
7.Scripps Florida, Scripps Res Inst, Dept Mol Therapeut, Jupiter, FL 33458 USA;
推荐引用方式
GB/T 7714		 He, Yuanzheng,Gao, Xiang,Goswami, Devrishi,et al. Molecular assembly of rhodopsin with G protein-coupled receptor kinases[J]. CELL RESEARCH,2017,27(6):728-747.
APA He, Yuanzheng.,Gao, Xiang.,Goswami, Devrishi.,Hou, Li.,Pal, Kuntal.,...&Xu, H. Eric.(2017).Molecular assembly of rhodopsin with G protein-coupled receptor kinases.CELL RESEARCH,27(6),728-747.
MLA He, Yuanzheng,et al."Molecular assembly of rhodopsin with G protein-coupled receptor kinases".CELL RESEARCH 27.6(2017):728-747.

入库方式： OAI收割

来源：上海药物研究所

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