molecularassemblyofrhodopsinwithgproteincoupledreceptorkinases
文献类型：期刊论文
| 作者 | He Yuanzheng1; Gao Xiang1; Goswami Devrishi2; Hou Li3 ; Pal Kuntal1; Yin Yanting1; Zhao Gongpu4; Ernst Oliver P5; Griffin Patrick2; Melcher Karsten1
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| 刊名 | cellresearch
 |
| 出版日期 | 2017 |
| 卷号 | 27期号:6页码:728 |
| 关键词 | rhodopsin GPCR GRK1 GRK5 Q41L |
| ISSN号 | 1001-0602 |
| DOI | 10.1038/cr.2017.72 |
| 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/GRKl interaction and provide a framework for understanding GRK-mediated desensitization of GPCRs. |
| 语种 | 英语 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/285115]  |
| 专题 | 中国科学院上海药物研究所 |
| 作者单位 | 1.Laboratory of Structural Sciences, Center for Structural Biology and Drug Discovery, Van Andel Research Institute 2.Department of Molecular Therapeutics, The Scripps Research Institute, Scripps Florida 3.中国科学院上海药物研究所 4.The Cryo-EM Core, Van Andel Research Institute 5.多伦多大学 |
| 推荐引用方式 GB/T 7714 | He Yuanzheng,Gao Xiang,Goswami Devrishi,et al. molecularassemblyofrhodopsinwithgproteincoupledreceptorkinases[J]. cellresearch,2017,27(6):728. |
| APA | He Yuanzheng.,Gao Xiang.,Goswami Devrishi.,Hou Li.,Pal Kuntal.,...&Xu H Eric.(2017).molecularassemblyofrhodopsinwithgproteincoupledreceptorkinases.cellresearch,27(6),728. |
| MLA | He Yuanzheng,et al."molecularassemblyofrhodopsinwithgproteincoupledreceptorkinases".cellresearch 27.6(2017):728. |
入库方式： OAI收割
来源：上海药物研究所
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