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Journal of Virology, June 2001, p. 5541-5549, Vol. 75, No. 12
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.12.5541-5549.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Mapping the Determinants of the CCR5 Amino-Terminal Sulfopeptide Interaction with Soluble Human Immunodeficiency Virus Type 1 gp120-CD4 Complexes

Emmanuel G. Cormier,1 Diep N. H. Tran,2 Liyana Yukhayeva,1 William C. Olson,2 and Tatjana Dragic1,*

Microbiology and Immunology Department, Albert Einstein College of Medicine, Bronx, New York 10461,1 and Progenics Pharmaceuticals, Inc., Tarrytown, New York 105912

Received 4 January 2001/Accepted 16 March 2001

CD4 and CCR5 mediate fusion and entry of R5 human immunodeficiency virus type 1 (HIV-1) strains. Sulfotyrosine and other negatively charged residues in the CCR5 amino-terminal domain (Nt) are crucial for gp120 binding and viral entry. We previously showed that a soluble gp120-CD4 complex specifically binds to a peptide corresponding to CCR5 Nt residues 2 to 18, with sulfotyrosines in positions 10 and 14. This sulfopeptide also inhibits soluble gp120-CD4 binding to cell surface CCR5 as well as infection by an R5 virus. Here we show that residues 10 to 18 constitute the minimal domain of the CCR5 Nt that is able to specifically interact with soluble gp120-CD4 complexes. In addition to sulfotyrosines in positions 10 and 14, negatively charged residues in positions 11 and 18 participate in this interaction. Furthermore, the CCR5 Nt binds to a CD4-induced surface on gp120 that is composed of conserved residues in the V3 loop stem and the C4 domain. Binding of gp120 to cell surface CCR5 is further influenced by residues in the crown of the V3 loop, C1, C2, and C3. Our data suggest that gp120 docking to CCR5 is a multistep process involving several independent regions of the envelope glycoprotein and the coreceptor.

* Corresponding author. Mailing address: Albert Einstein College of Medicine, Microbiology and Immunology Department, 1300 Morris Park Ave., Bronx, NY 10461. Phone: (718) 430-3282. Fax: (718) 430-8711. E-mail: tdragic{at}aecom.yu.edu.

Journal of Virology, June 2001, p. 5541-5549, Vol. 75, No. 12
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.12.5541-5549.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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