Restricted variable residues in the c-terminal segment of hiv-1v3 loop regulate the molecular anatomy of ccr5 utilization | |
Hu, QX; Napier, KB; Trent, JO; Wang, ZX; Taylor, S; Griffin, GE; Peiper, SC; Shattock, RJ | |
刊名 | Journal of molecular biology
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2005-07-22 | |
卷号 | 350期号:4页码:699-712 |
关键词 | Hiv-1 Envelope glycoprotein V3 loop Ccr5 Structure |
ISSN号 | 0022-2836 |
DOI | 10.1016/j.jmb.2005.05.024 |
通讯作者 | Shattock, rj() |
英文摘要 | The v3 loop of the hiv-1 envelope glycoprotein (env) is the major determinant for coreceptor utilization, but the structural basis for this specificity remains to be defined. by characterizing a set of naturally occurring r5 env variants, we demonstrate that asp324 in the conserved iigdir motif of the v3 loop (ctrpn(300)nntrksihigp(311)grafytt geiigd(324)irqahc) c-terminal segment regulates the molecular anatomy of ccr5 utilization. whereas gp120 subunits with asp or 324 were fusogenic with coreceptor chimeras containing either the n-terminal domain or the body of ccr5, substitution of charged (glu, lys) or small hydrophobic (gly, ala) residues resulted in complete loss of fusogenic activity with the n terminus and markedly reduced utilization of the body of ccr5, although their ability to use wild-type ccr5 was unchanged. this phenotypic conversion was confirmed in both gain and loss of function experiments using env from multiple subtypes. alignment of sequences of r5 v3 loops (n = 599) from the hiv database revealed that the mutation of asp324 in the conserved iigdir motif is restricted to asn324, with proportions of 71.5% and 28%, respectively. infection of primary cd4+t cells demonstrated that env bearing asp324 was less sensitive to rantes, suggesting that asp or asn in this position may be crucial for viral fitness. the cd4-dependent gp120 binding to ccr5 was decreased when asp324 was replaced with a charged or hydrophobic residue, but unchanged when replaced with asn. molecular modeling analyses predicted that asp/asn324 forms a critical h-bond with asn300. these findings indicate that asp or asn at position 324 of the v3 stem stabilizes the conformation of v3 loop and hence influences the intensities of interaction between cd4-activated gp120 and ccr5 which results in viral entry. (c) 2005 elsevier ltd. all rights reserved. |
WOS关键词 | IMMUNODEFICIENCY-VIRUS TYPE-1 ; GP120 ENVELOPE GLYCOPROTEIN ; CHEMOKINE RECEPTOR ; V3 LOOP ; CORECEPTOR UTILIZATION ; DISTINCT CCR5 ; CELL TROPISM ; BINDING ; INFECTION ; DETERMINANTS |
WOS研究方向 | Biochemistry & Molecular Biology |
WOS类目 | Biochemistry & Molecular Biology |
语种 | 英语 |
出版者 | ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD |
WOS记录号 | WOS:000230446000008 |
内容类型 | 期刊论文 |
URI标识 | http://www.corc.org.cn/handle/1471x/2375206 |
专题 | 武汉病毒研究所 |
通讯作者 | Shattock, RJ |
作者单位 | 1.Univ Louisville, James Graham Brown Canc Ctr, JG Brown Modeling Facil, Louisville, KY 40202 USA 2.St Georges Univ London, Dept Cellular & Mol Med, Div Infect Dis, London SW17 0RE, England 3.Chinese Acad Sci, Wuhan Inst Virol, Wuhan 430071, Peoples R China 4.Univ Louisville, James Graham Brown Canc Ctr, JG Brown Modeling Facil, Louisville, KY 40202 USA 5.Med Coll Georgia, Dept Pathol, Augusta, GA 30912 USA 6.Univ Birmingham, Div Immun & Infect, Birmingham B9 5SS, W Midlands, England |
推荐引用方式 GB/T 7714 | Hu, QX,Napier, KB,Trent, JO,et al. Restricted variable residues in the c-terminal segment of hiv-1v3 loop regulate the molecular anatomy of ccr5 utilization[J]. Journal of molecular biology,2005,350(4):699-712. |
APA | Hu, QX.,Napier, KB.,Trent, JO.,Wang, ZX.,Taylor, S.,...&Shattock, RJ.(2005).Restricted variable residues in the c-terminal segment of hiv-1v3 loop regulate the molecular anatomy of ccr5 utilization.Journal of molecular biology,350(4),699-712. |
MLA | Hu, QX,et al."Restricted variable residues in the c-terminal segment of hiv-1v3 loop regulate the molecular anatomy of ccr5 utilization".Journal of molecular biology 350.4(2005):699-712. |
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