Cholesterol-beta(1)AR interaction versus cholesterol-beta(2)AR interaction

doi:10.1002/prot.24456

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药物发现与设计中心

	Cholesterol-beta(1)AR interaction versus cholesterol-beta(2)AR interaction
	Cang, Xiaohui 1,2; Yang, Linlin 1; Yang, Jing 1; Luo, Cheng1 ; Zheng, Mingyue1 ; Yu, Kunqian1 ; Yang, Huaiyu 1; Jiang, Hualiang1
刊名	PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
	2014-05
卷号	82 期号:5 页码:760-770
关键词	cholesterol-binding site beta-adrenergic receptor molecular dynamics simulation G protein-coupled receptor
ISSN号	0887-3585
DOI	10.1002/prot.24456
文献子类	Article
英文摘要	Two 8-ms all-atom molecular dynamics simulations have been performed on the two highly homologous G protein-coupled receptor (GPCR) subtypes, beta 1- and beta 2-adrenergic receptors, which were embedded in a lipid bilayer with randomly dispersed cholesterol molecules. During the simulations, cholesterol molecules accumulate to different surface regions of the two receptors, suggesting the subtype specificity of cholesterol-beta-adrenergic receptor interaction and providing some clues to the physiological difference of the two subtypes. Meanwhile, comparison between the two receptors in interacting with cholesterols shed some new light on general determinants of cholesterol binding to GPCRs. Our results indicate that although the concave surface, charged residues and aromatic residues are important, neither of these stabilizing factors is indispensable for a cholesterol interaction site. Different combinations of these factors lead to the diversified binding modes of cholesterol binding to the receptors. Our long-time simulations, for the first time, revealed the pathway of a cholesterol molecule entering the consensus cholesterol motif (CCM) site, and the binding process of cholesterol to CCM is accompanied by a side chain flipping of the conserved Trp4.50. Moreover, the simulation results suggest that the I-/V-/L-rich region on the extracellular parts of helix 6 might be an alternatively conserved cholesterol-binding site for the class-A GPCRs. (C) 2013 Wiley Periodicals, Inc.
资助项目	State Key Program of Basic Research of China[2012CB518005] ; National Natural Science Foundation of China[81230076] ; National Natural Science Foundation of China[31100594] ; Shanghai Science and Technology Development Funds[12QA1404000] ; Shanghai Science and Technology Development Funds[11ZR1444400] ; SA-SIBS Scholarship Program[00000000] ; National Science and Technology Major Project "Key New Drug Creation and Manufacturing Program"[2013ZX09507001]
WOS关键词	PROTEIN-COUPLED RECEPTORS ; MOLECULAR-DYNAMICS SIMULATIONS ; A(2A) ADENOSINE RECEPTOR ; ADRENOCEPTOR SIGNALING PATHWAYS ; SEROTONIN(1A) RECEPTOR ; MEMBRANE CHOLESTEROL ; CRYSTAL-STRUCTURE ; INTERACTION SITES ; STRUCTURAL BASIS ; BINDING-SITES
WOS研究方向	Biochemistry & Molecular Biology ; Biophysics
语种	英语
出版者	WILEY
WOS记录号	WOS:000337280400007
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277087]
专题	药物发现与设计中心中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Yang, Huaiyu
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.Zhejiang Univ, Inst Genet, Coll Life Sci, Hangzhou 310058, Zhejiang, Peoples R China
推荐引用方式 GB/T 7714	Cang, Xiaohui,Yang, Linlin,Yang, Jing,et al. Cholesterol-beta(1)AR interaction versus cholesterol-beta(2)AR interaction[J]. PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS,2014,82(5):760-770.
APA	Cang, Xiaohui.,Yang, Linlin.,Yang, Jing.,Luo, Cheng.,Zheng, Mingyue.,...&Jiang, Hualiang.(2014).Cholesterol-beta(1)AR interaction versus cholesterol-beta(2)AR interaction.PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS,82(5),760-770.
MLA	Cang, Xiaohui,et al."Cholesterol-beta(1)AR interaction versus cholesterol-beta(2)AR interaction".PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS 82.5(2014):760-770.