Science (American Association for the Advancement of Science), 2010-08, Vol.329 (5993), p.811-817
2010
Details
- Autor(en) / Beteiligte
- Titel
- Structural Basis for Broad and Potent Neutralization of HIV-1 by Antibody VRC01
- Ist Teil von
- Science (American Association for the Advancement of Science), 2010-08, Vol.329 (5993), p.811-817
- Ort / Verlag
- United States: American Association for the Advancement of Science
- Erscheinungsjahr
- 2010
- Link zum Volltext
- Quelle
- American Association for the Advancement of Science
- Beschreibungen/Notizen
- During HIV-1 infection, antibodies are generated against the region of the viral gp120 envelope glycoprotein that binds CD4, the primary receptor for HIV-1. Among these antibodies, VRC01 achieves broad neutralization of diverse viral strains. We determined the crystal structure of VRC01 in complex with a human immunodeficiency virus HIV-1 gp120 core. VRC01 partially mimics CD4 interaction with gp120. A shift from the CD4-defined orientation, however, focuses VRC01 onto the vulnerable site of initial CD4 attachment, allowing it to overcome the glycan and conformational masking that diminishes the neutralization potency of most CD4-binding-site antibodies. To achieve this recognition, VRC01 contacts gp120 mainly through immunoglobulin V-gene regions substantially altered from their genomic precursors. Partial receptor mimicry and extensive affinity maturation thus facilitate neutralization of HIV-1 by natural human antibodies.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0036-8075eISSN: 1095-9203DOI: 10.1126/science.1192819Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2981354
- Format
- –
- Schlagworte
- AIDS Vaccines, Amino Acid Sequence, Antibodies, Antibodies, Neutralizing - chemistry, Antibodies, Neutralizing - immunology, Antibody Affinity, Antigenic Variation, Base Sequence, Binding Sites, Antibody, CD4 Antigens - chemistry, CD4 Antigens - immunology, CD4 Antigens - metabolism, Crystal structure, Crystallography, X-Ray, Epitopes - immunology, Genomics, HIV, HIV 1, HIV Antibodies - chemistry, HIV Antibodies - immunology, HIV Envelope Protein gp120 - chemistry, HIV Envelope Protein gp120 - genetics, HIV Envelope Protein gp120 - immunology, HIV-1 - immunology, Human immunodeficiency virus, Human immunodeficiency virus 1, Humans, Hydrogen bonds, Immune system, Immunoglobulin Fab Fragments - chemistry, Immunoglobulin Fab Fragments - immunology, Immunoglobulin Fab Fragments - metabolism, Immunoglobulins, Infections, Models, Molecular, Molecular biology, Molecular Mimicry, Molecular Sequence Data, Neutralization Tests, Neutralizing antibodies, Polysaccharides, Protein Conformation, Protein Structure, Tertiary, Receptors, Viruses