Cholesterol-beta(1)AR interaction versus cholesterol-beta(2)AR interaction
文献类型：期刊论文
| 作者 | Cang, Xiaohui1,2; Yang, Linlin1; Yang, Jing1; Luo, Cheng1 ; Zheng, Mingyue1; Yu, Kunqian1; Yang, Huaiyu1; Jiang, Hualiang1
|
| 刊名 | PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
 |
| 出版日期 | 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. |
| 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 |
| 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研究方向 | Biochemistry & Molecular Biology ; Biophysics |
| 语种 | 英语 |
| WOS记录号 | WOS:000337280400007 |
| 出版者 | WILEY |
| 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. |
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。