Abstract
We present the crystal structure at 2.7 angstrom resolution of the human antibody IgG1 b12. Antibody b12 recognizes the CD4-binding site of human immunodeficiency virus-1 (HIV-1) gp120 and is one of only two known antibodies against gp120 capable of broad and potent neutralization of primary HIV-1 isolates. A key feature of the antibody-combining site is the protruding, finger-like long CDR H3 that can penetrate the recessed CD4-binding site of gp120. A docking model of b12 and gp120 reveals severe structural constraints that explain the extraordinary challenge in eliciting effective neutralizing antibodies similar to b12. The structure, together with mutagenesis studies, provides a rationale for the extensive cross-reactivity of b12 and a valuable framework for the design of HIV-1 vaccines capable of eliciting b12-like activity.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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AIDS Vaccines
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Amino Acid Sequence
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Binding Sites
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Binding Sites, Antibody
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CD4 Antigens / metabolism
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Complementarity Determining Regions / chemistry
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Crystallography, X-Ray
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Epitopes
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HIV Antibodies / chemistry*
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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 / immunology*
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Humans
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Hydrogen Bonding
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Immunoglobulin G / chemistry*
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Immunoglobulin G / immunology
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Models, Molecular
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Molecular Sequence Data
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Neutralization Tests
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Peptide Library
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Protein Conformation
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Protein Structure, Tertiary
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Templates, Genetic
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Thermodynamics
Substances
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AIDS Vaccines
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CD4 Antigens
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Complementarity Determining Regions
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Epitopes
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HIV Antibodies
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HIV Envelope Protein gp120
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Immunoglobulin G
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Peptide Library