Structural definition of a conserved neutralization epitope on HIV-1 gp120
Open accessAbstract
The remarkable diversity, glycosylation and conformational flexibility of the human immunodeficiency virus type 1 (HIV-1) envelope (Env), including substantial rearrangement of the gp120 glycoprotein upon binding the CD4 receptor, allow it to evade antibody-mediated neutralization. Despite this complexity, the HIV-1 Env must retain conserved determinants that mediate CD4 binding. To evaluate how these determinants might provide opportunities for antibody recognition, we created variants of gp120 stabilized in the CD4-bound state, assessed binding of CD4 and of receptor-binding-site antibodies, and determined the structure at 2.3 A resolution of the broadly neutralizing antibody b12 in complex with gp120. b12 binds to a conformationally invariant surface that overlaps a distinct subset of the CD4-binding site. This surface is involved in the metastable attachment of CD4, before the gp120 rearrangement required for stable engagement. A site of vulnerability, related to a functional requirement for efficient association with CD4, can therefore be targeted by antibody to neutralize HIV-1.
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Structure-based design of epitopes recognized by template neutralizing antibodies can engineer antigenicity.
“We and others have engineered antigenicity (13-17) through structure-based design of the epitopes recognized by template neutralizing antibodies.”
From Structure-Based Design of a Fusion Glycoprotein Vaccine for Respiratory Syncytial Virus (2013) · cites this paper as [14]
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- Authors
- Zhou, T., Xu, L., Dey, B., Hessell, A. J., Van Ryk, D., Xiang, S.-H., Yang, X., Zhang, M.-Y., Zwick, M. B., Arthos, J., Burton, D. R., Dimitrov, D. S., Sodroski, J., Wyatt, R., Nabel, G. J., & Kwong, P. D.
- Affiliations
- National Institutes of Health (US)
- Scripps Research Institute (US)
- Harvard University (US)
- Corresponding author
- Kwong, Peter D.
- ORCID
- Venue
- Nature
- Published
- 2007-02-15
- Volume
- 445
- Issue
- 7129
- Pages
- 732-737
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2584968
- OpenAlex
- W2080089116
- Cited by
- 770
- References
- 49
- Citations by year
- 2026: 8 · 2025: 6 · 2024: 17 · 2023: 6 · 2022: 7 · 2021: 14 · 2020: 12 · 2019: 19 · 2018: 25 · 2017: 35 · 2016: 34 · 2015: 41 · 2014: 40 · 2013: 77 · 2012: 90
- FWCI
- 30.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Lincoln (University of Nebraska) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Funders
- U.S. Department of Energy
- Bill and Melinda Gates Foundation
- International AIDS Vaccine Initiative
- National Institutes of Health
- Office of Science
- National Institute of Allergy and Infectious Diseases (U19AI067854)
- Basic Energy Sciences
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Physical Sciences › Chemistry › Organic Chemistry › Carbohydrate Chemistry and Synthesis
- Keywords
- HIV-1, gp120, CD4 binding site, CD4 receptor, antibody neutralization, conformational flexibility, antibody-antigen complex structure
- MeSH terms
- Epitopes, Binding Sites, Models, Molecular, Molecular Weight, Neutralization Tests, Protein Conformation, HIV Antibodies, HIV-1, HIV Envelope Protein gp120, CD4 Antigens, Conserved Sequence
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