Evaluation of chemical cross-linkers for in-depth structural analysis of G protein-coupled receptors through cross-linking mass spectrometry

doi:10.1016/j.aca.2019.12.036

	Evaluation of chemical cross-linkers for in-depth structural analysis of G protein-coupled receptors through cross-linking mass spectrometry
	Xia, Lisha1,2,3,4 ; Ma, Ziliang1,2,3,4 ; Tong, Jiahui1,2 ; Tang, Yuliang 5,6; Li, Shanshan1 ; Qin, Shanshan1 ; Lou, Ronghui1,2 ; Zhao, Suwen1,2 ; Lei, Xiaoguang 5,6; Shui, Wenqing1,2
	2020-03-15
发表期刊	ANALYTICA CHIMICA ACTA
ISSN	0003-2670
EISSN	1873-4324
卷号	1102 页码:53-62
发表状态	已发表
DOI	10.1016/j.aca.2019.12.036
摘要	Chemical cross-linking would conceivably cause structural disruption of a protein, but few cross-linkers have been fully evaluated in this aspect. Furthermore, integral membrane proteins may differ from soluble proteins in the selection of suitable cross-linkers, which has never been investigated. In this study, we systematically evaluated the impact of five conventional cross-linkers targeting Lys, Asp and Glu, and two Arg-reactive cross-linkers on the structural and functional integrity of two G protein-coupled receptors (GPCRs). Perturbation of the receptor structure and ligand-binding activity was observed, depending on the receptor and cross-linking conditions. In particular, our study demonstrated that the concentrations of PDH and KArGO need to be fine-tuned in order to minimize the structural and functional disturbance of specific GPCRs. A set of amenable cross-linkers was selected to acquire the most comprehensive cross-link maps for two GPCRs. Our in-depth cross-linking mass spectrometry (CXMS) analysis has revealed dynamic features of structural regions in GPCRs that are not observable in the crystal structures. Thus, CXMS analysis of GPCRs using the expanded toolkit would facilitate structural modeling of uncharacterized receptors and gain new insights into receptor-ligand interactions. (C) 2019 Elsevier B.V. All rights reserved.
关键词	Cross-linking mass spectrometry chemical cross-linker GPCR Integral membrane protein structural dynamics
收录类别	SCI ; SCIE
语种	英语
资助项目	National High Technology Project 973[2015CB856200]
WOS研究方向	Chemistry
WOS类目	Chemistry, Analytical
WOS记录号	WOS:000512982100006
出版者	ELSEVIER
WOS关键词	ADENOSINE A(2A) RECEPTOR ; MOLECULAR-DYNAMICS SIMULATIONS ; CRYO-EM STRUCTURE ; CRYSTAL-STRUCTURE ; AMBER ; IDENTIFICATION ; ASSEMBLIES ; NANODISCS ; COMPLEX
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/105386
专题	生命科学与技术学院_硕士生 iHuman研究所_PI研究组_赵素文组 iHuman研究所_PI研究组_水雯箐组生命科学与技术学院_博士生
通讯作者	Lei, Xiaoguang; Shui, Wenqing
作者单位	1.ShanghaiTech Univ, iHuman Inst, Shanghai 201210, Peoples R China 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 3.Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China 4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 5.Peking Univ, Synthet & Funct Biomol Ctr, Coll Chem & Mol Engn,Key Lab Bioorgan Chem & Mol, Minist Educ,Beijing Natl Lab Mol Sci,Dept Chem Bi, Beijing 10087, Peoples R China 6.Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing 10087, Peoples R China
第一作者单位	iHuman研究所; 生命科学与技术学院
通讯作者单位	iHuman研究所; 生命科学与技术学院
第一作者的第一单位	iHuman研究所
推荐引用方式 GB/T 7714	Xia, Lisha,Ma, Ziliang,Tong, Jiahui,et al. Evaluation of chemical cross-linkers for in-depth structural analysis of G protein-coupled receptors through cross-linking mass spectrometry[J]. ANALYTICA CHIMICA ACTA,2020,1102:53-62.
APA	Xia, Lisha.,Ma, Ziliang.,Tong, Jiahui.,Tang, Yuliang.,Li, Shanshan.,...&Shui, Wenqing.(2020).Evaluation of chemical cross-linkers for in-depth structural analysis of G protein-coupled receptors through cross-linking mass spectrometry.ANALYTICA CHIMICA ACTA,1102,53-62.
MLA	Xia, Lisha,et al."Evaluation of chemical cross-linkers for in-depth structural analysis of G protein-coupled receptors through cross-linking mass spectrometry".ANALYTICA CHIMICA ACTA 1102(2020):53-62.