Structural and functional characterization of the human CCR5 receptor in complex with HIV gp120 envelope glycoprotein and CD4 receptor by molecular modeling studies

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	Structural and functional characterization of the human CCR5 receptor in complex with HIV gp120 envelope glycoprotein and CD4 receptor by molecular modeling studies
	Liu SQ 1; Shi XF 2; Sun ZR*1; sunzhr@mail.tsinghua.edu.cn
	2003
发表期刊	JOURNAL OF MOLECULAR MODELING
ISSN	0948-5023
卷号	9 期号:5 页码:329-336
合作性质	其它
摘要	The entry of human immunodeficiency virus (HIV) into cells depends on a sequential interaction of the gp120 envelope glycoprotein with the cellular receptors CD4 and members of the chemokine receptor family. The CC chemokine receptor CCR5 is such a receptor for several chemokines and a major coreceptor for the entry of R5 HIV type-1 (HIV-1) into cells. Although many studies focus on the interaction of CCR5 with HIV-1, the corresponding interaction sites in CCR5 and gp120 have not been matched. Here we used an approach combining protein structure modeling, docking and molecular dynamics simulation to build a series of structural models of the CCR5 in complexes with gp120 and CD4. Interactions such as hydrogen bonds, salt bridges and van der Waals contacts between CCR5 and gp120 were investigated. Three snapshots of CCR5-gp120-CD4 models revealed that the initial interactions of CCR5 with gp120 are involved in the negatively charged N-terminus (Nt) region of CCR5 and positively charged bridging sheet region of gp120. Further interactions occurred between extracellular loop2 (ECL2) of CCR5 and the base of V3 loop regions of gp120. These interactions may induce the conformational changes in gp120 and lead to the final entry of HIV into the cell. These results not only strongly support the two-step gp120-CCR5 binding mechanism, but also rationalize extensive biological data about the role of CCR5 in HIV-1 gp120 binding and entry, and may guide efforts to design novel inhibitors.
关键词	Ccr5 Gp120 Interaction Docking Molecular Dynamics Simulation Complex
资助者	This work was supported in part by the National Natural Science Grant (China) (No. 19947006) and partially by the National Key Foundation Research Grant (No. 2002AA231031) in China (863) ; This work was supported in part by the National Natural Science Grant (China) (No. 19947006) and partially by the National Key Foundation Research Grant (No. 2002AA231031) in China (863) ; This work was supported in part by the National Natural Science Grant (China) (No. 19947006) and partially by the National Key Foundation Research Grant (No. 2002AA231031) in China (863) ; This work was supported in part by the National Natural Science Grant (China) (No. 19947006) and partially by the National Key Foundation Research Grant (No. 2002AA231031) in China (863)
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收录类别	SCI
语种	英语
资助者	This work was supported in part by the National Natural Science Grant (China) (No. 19947006) and partially by the National Key Foundation Research Grant (No. 2002AA231031) in China (863) ; This work was supported in part by the National Natural Science Grant (China) (No. 19947006) and partially by the National Key Foundation Research Grant (No. 2002AA231031) in China (863) ; This work was supported in part by the National Natural Science Grant (China) (No. 19947006) and partially by the National Key Foundation Research Grant (No. 2002AA231031) in China (863) ; This work was supported in part by the National Natural Science Grant (China) (No. 19947006) and partially by the National Key Foundation Research Grant (No. 2002AA231031) in China (863)
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/5295
专题	其他细胞与分子进化重点实验室
通讯作者	sunzhr@mail.tsinghua.edu.cn
作者单位	1.Institue of Bioinformatics, Department of Biological Sciences and Biotechnology, Tsinghua University, 100084 Beijing, People’s Republic of China 2.Cellular and Molecular Evolutionary Key Laboratory, Kunming Institute of Zoology, Chinese Academy of Sciences, 650223 Kunming, People’s Republic of China
推荐引用方式 GB/T 7714	Liu SQ,Shi XF,Sun ZR*,et al. Structural and functional characterization of the human CCR5 receptor in complex with HIV gp120 envelope glycoprotein and CD4 receptor by molecular modeling studies[J]. JOURNAL OF MOLECULAR MODELING,2003,9(5):329-336.
APA	Liu SQ,Shi XF,Sun ZR*,&sunzhr@mail.tsinghua.edu.cn.(2003).Structural and functional characterization of the human CCR5 receptor in complex with HIV gp120 envelope glycoprotein and CD4 receptor by molecular modeling studies.JOURNAL OF MOLECULAR MODELING,9(5),329-336.
MLA	Liu SQ,et al."Structural and functional characterization of the human CCR5 receptor in complex with HIV gp120 envelope glycoprotein and CD4 receptor by molecular modeling studies".JOURNAL OF MOLECULAR MODELING 9.5(2003):329-336.

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