中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
Structural Mass Spectrometry Captures Residue-Resolved Comprehensive Conformational Rearrangements of a G Protein-Coupled Receptor

文献类型：期刊论文

作者Liu, Hongyue4,5,6; Yan, Pengfei4,5,6; Zhang, Zhaoyu4,5,6; Han, Hongbo3,4; Zhou, Qingtong2; Zheng, Jie3,4; Zhang, Jian1; Xu, Fei5,6; Shui, Wenqing5,6
刊名JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
出版日期2024-07-13
卷号146期号:29页码:20045-20058
ISSN号0002-7863
DOI10.1021/jacs.4c03922
通讯作者Xu, Fei(xufei@shanghaitech.edu.cn) ; Shui, Wenqing(shuiwq@shanghaitech.edu.cn)
英文摘要G protein-coupled receptor (GPCR) structural studies with in-solution spectroscopic approaches have offered distinctive insights into GPCR activation and signaling that highly complement those yielded from structural snapshots by crystallography or cryo-EM. While most current spectroscopic approaches allow for probing structural changes at selected residues or loop regions, they are not suitable for capturing a holistic view of GPCR conformational rearrangements across multiple domains. Herein, we develop an approach based on limited proteolysis mass spectrometry (LiP-MS) to simultaneously monitor conformational alterations of a large number of residues spanning both flexible loops and structured transmembrane domains for a given GPCR. To benchmark LiP-MS for GPCR conformational profiling, we studied the adenosine 2A receptor (A(2A)R) in response to different ligand binding (agonist/antagonist/allosteric modulators) and G protein coupling. Systematic and residue-resolved profiling of A(2A)R conformational rearrangements by LiP-MS precisely captures structural mechanisms in multiple domains underlying ligand engagement, receptor activation, and allostery, and may also reflect local conformational flexibility. Furthermore, these residue-resolution structural fingerprints of the A(2A)R protein allow us to readily classify ligands of different pharmacology and distinguish the G protein-coupled state. Thus, our study provides a new structural MS approach that would be generalizable to characterizing conformational transition and plasticity for challenging integral membrane proteins.
WOS关键词ADENOSINE A(2A) RECEPTOR ; BINDING ; INSIGHTS ; ACTIVATION ; DYNAMICS ; COMPLEX
资助项目National Key R&D Program of China[2022YFA1302902] ; National Key R&D Program of China[32171439] ; National Key R&D Program of China[32071194] ; National Natural Science Foundation of China ; Shanghai Tech University, Shanghai Frontiers Science Center for Biomacromolecules and Precision Medicine at Shanghai Tech University ; STI2030-Major Project[2021ZD0203400]
WOS研究方向Chemistry
语种英语
WOS记录号WOS:001276278800001
出版者AMER CHEMICAL SOC
源URL[http://119.78.100.183/handle/2S10ELR8/312547]  
专题中国科学院上海药物研究所
通讯作者Xu, Fei; Shui, Wenqing
作者单位1.Shanghai Jiao Tong Univ, Sch Med, Med Chem & Bioinformat Ctr, Shanghai 200025, Peoples R China
2.Fudan Univ, Sch Basic Med Sci, Dept Pharmacol, Shanghai 200032, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
5.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
6.ShanghaiTech Univ, iHuman Inst, Shanghai 201210, Peoples R China
推荐引用方式
GB/T 7714		 Liu, Hongyue,Yan, Pengfei,Zhang, Zhaoyu,et al. Structural Mass Spectrometry Captures Residue-Resolved Comprehensive Conformational Rearrangements of a G Protein-Coupled Receptor[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,2024,146(29):20045-20058.
APA Liu, Hongyue.,Yan, Pengfei.,Zhang, Zhaoyu.,Han, Hongbo.,Zhou, Qingtong.,...&Shui, Wenqing.(2024).Structural Mass Spectrometry Captures Residue-Resolved Comprehensive Conformational Rearrangements of a G Protein-Coupled Receptor.JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,146(29),20045-20058.
MLA Liu, Hongyue,et al."Structural Mass Spectrometry Captures Residue-Resolved Comprehensive Conformational Rearrangements of a G Protein-Coupled Receptor".JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 146.29(2024):20045-20058.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

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。