Abstract
The third variable region (V3) of the HIV-1 gp120 envelope glycoprotein is immunodominant and contains features essential for coreceptor binding. We determined the structure of V3 in the context of an HIV-1 gp120 core complexed to the CD4 receptor and to the X5 antibody at 3.5 angstrom resolution. Binding of gp120 to cell-surface CD4 would position V3 so that its coreceptor-binding tip protrudes 30 angstroms from the core toward the target cell membrane. The extended nature and antibody accessibility of V3 explain its immunodominance. Together, the results provide a structural rationale for the role of V3 in HIV entry and neutralization.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, N.I.H., Intramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Binding Sites
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CD4 Antigens / chemistry
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CD4 Antigens / metabolism*
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Crystallization
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Crystallography, X-Ray
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HIV Antibodies / immunology
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HIV Envelope Protein gp120 / chemistry*
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HIV Envelope Protein gp120 / immunology
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HIV Envelope Protein gp120 / metabolism
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HIV-1 / chemistry*
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HIV-1 / immunology
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HIV-1 / metabolism
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Humans
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Hydrogen Bonding
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Immunodominant Epitopes
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Models, Molecular
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Molecular Sequence Data
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Peptide Fragments / chemistry*
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Peptide Fragments / immunology
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Peptide Fragments / metabolism
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Protein Binding
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Protein Conformation
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Protein Structure, Tertiary
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Receptors, CCR5 / chemistry
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Receptors, CCR5 / metabolism
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Receptors, CXCR4 / chemistry
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Receptors, CXCR4 / metabolism
Substances
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CD4 Antigens
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HIV Antibodies
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HIV Envelope Protein gp120
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HIV envelope protein gp120 (305-321)
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Immunodominant Epitopes
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Peptide Fragments
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Receptors, CCR5
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Receptors, CXCR4