Mapping the determinants of the CCR5 amino-terminal sulfopeptide interaction with soluble human immunodeficiency virus type 1 gp120-CD4 complexes.
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.
Cormier
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EG
Microbiology and Immunology Department, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Tran
D N
DN
Yukhayeva
L
L
Olson
W C
WC
Dragic
T
T
D000577:Amides / Q000378:metabolism; D000603:Amino Acids, Sulfur / Q000737:chemistry* / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism*; D018925:Chemokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D000644:Quaternary Ammonium Compounds / Q000378:metabolism; D019713:Receptors, CCR5 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020349:Surface Plasmon Resonance
D000577:Amides; D000603:Amino Acids, Sulfur; D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D018925:Chemokines; D015699:HIV Envelope Protein gp120; D007074:Immunoglobulin G; D010455:Peptides; D000644:Quaternary Ammonium Compounds; D019713:Receptors, CCR5; C119369:TAK 779