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PMID: 11356961 Published · ppublish English Evaluation Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Mapping the determinants of the CCR5 amino-terminal sulfopeptide interaction with soluble human immunodeficiency virus type 1 gp120-CD4 complexes.

Journal of virology ·Vol. 75 ·No. 12 ·2001-06-00 ·Pages 5541-9

Cormier EG, Tran DN, Yukhayeva L, Olson WC, Dragic T

Abstract

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.

MeSH Terms
Amides/metabolism Amino Acids, Sulfur/chemistry,metabolism Antibodies, Monoclonal/metabolism CD4 Antigens/metabolism Chemokines/metabolism Enzyme-Linked Immunosorbent Assay/methods HIV Envelope Protein gp120/genetics,metabolism HIV-1/physiology Humans Immunoglobulin G/metabolism Peptides/chemistry,metabolism Quaternary Ammonium Compounds/metabolism Receptors, CCR5/chemistry,genetics,metabolism Surface Plasmon Resonance
Chemicals
Amides Amino Acids, Sulfur Antibodies, Monoclonal CD4 Antigens Chemokines HIV Envelope Protein gp120 Immunoglobulin G Peptides Quaternary Ammonium Compounds Receptors, CCR5 TAK 779
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Cormier E G
Microbiology and Immunology Department, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Tran D N
Yukhayeva L
Olson W C
Dragic T
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.75.12.5541-5549.2001
Published
2001-06-00
Pages
5541-9
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC114266
Subset
IM
Grants
NIAID NIH HHS · R01 AI043847 · United States
NIAID NIH HHS · R01 AI 43847 · United States
External Links
PubMed source DOI: 10.1128/JVI.75.12.5541-5549.2001 PMC Full Text View journal details
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