Structure of the CCR5 Chemokine Receptor-HIV Entry Inhibitor Maraviroc Complex

doi:10.1126/science.1241475

KMS > iHuman研究所 > 特聘教授组 > Raymond Stevens组

	Structure of the CCR5 Chemokine Receptor-HIV Entry Inhibitor Maraviroc Complex
	Tan, Qiuxiang 1; Zhu, Ya 1; Li, Jian 1; Chen, Zhuxi 2; Han, Gye Won 3; Kufareva, Irina 4; Li, Tingting 1; Ma, Limin 1; Fenalti, Gustavo 3; Li, Jing 1; Zhang, Wenru 1; Xie, Xin 1; Yang, Huaiyu 2; Jiang, Hualiang 2; Cherezov, Vadim 3; Liu, Hong 1; Stevens, Raymond C.1,3,5 ; Zhao, Qiang 1; Wu, Beili1
	2013-09-20
发表期刊	SCIENCE (IF:44.7[JCR-2023],50.3[5-Year])
ISSN	0036-8075
卷号	341 期号:6152 页码:1387-1390
发表状态	已发表
DOI	10.1126/science.1241475
摘要	The CCR5 chemokine receptor acts as a co-receptor for HIV-1 viral entry. Here we report the 2.7 angstrom-resolution crystal structure of human CCR5 bound to the marketed HIV drug maraviroc. The structure reveals a ligand-binding site that is distinct from the proposed major recognition sites for chemokines and the viral glycoprotein gp120, providing insights into the mechanism of allosteric inhibition of chemokine signaling and viral entry. A comparison between CCR5 and CXCR4 crystal structures, along with models of co-receptor-gp120-V3 complexes, suggests that different charge distributions and steric hindrances caused by residue substitutions may be major determinants of HIV-1 co-receptor selectivity. These high-resolution insights into CCR5 can enable structure-based drug discovery for the treatment of HIV-1 infection.
收录类别	SCI
语种	英语
资助项目	[R01 GM071872]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000324597200045
出版者	AMER ASSOC ADVANCEMENT SCIENCE
WOS关键词	CRYSTAL-STRUCTURE ; SMALL-MOLECULE ; CORECEPTOR ; BINDING ; DISCOVERY ; TERMINUS ; ANTIBODY
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/2452
专题	iHuman研究所_特聘教授组_Raymond Stevens组 iHuman研究所生命科学与技术学院_特聘教授组_吴蓓丽组
通讯作者	Wu, Beili
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China 3.Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA 4.Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA 5.ShanghaiTech Univ, iHuman Inst, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Tan, Qiuxiang,Zhu, Ya,Li, Jian,et al. Structure of the CCR5 Chemokine Receptor-HIV Entry Inhibitor Maraviroc Complex[J]. SCIENCE,2013,341(6152):1387-1390.
APA	Tan, Qiuxiang.,Zhu, Ya.,Li, Jian.,Chen, Zhuxi.,Han, Gye Won.,...&Wu, Beili.(2013).Structure of the CCR5 Chemokine Receptor-HIV Entry Inhibitor Maraviroc Complex.SCIENCE,341(6152),1387-1390.
MLA	Tan, Qiuxiang,et al."Structure of the CCR5 Chemokine Receptor-HIV Entry Inhibitor Maraviroc Complex".SCIENCE 341.6152(2013):1387-1390.