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Structural definition of a conserved neutralization epitope on HIV-1 gp120

Author

Listed:
  • Tongqing Zhou

    (Vaccine Research Center, and,)

  • Ling Xu

    (Vaccine Research Center, and,)

  • Barna Dey

    (Vaccine Research Center, and,)

  • Ann J. Hessell

    (Scripps Research Institute, La Jolla, California 92037, USA)

  • Donald Van Ryk

    (Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • Shi-Hua Xiang

    (Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA)

  • Xinzhen Yang

    (Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA)

  • Mei-Yun Zhang

    (Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702, USA)

  • Michael B. Zwick

    (Scripps Research Institute, La Jolla, California 92037, USA)

  • James Arthos

    (Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • Dennis R. Burton

    (Scripps Research Institute, La Jolla, California 92037, USA)

  • Dimiter S. Dimitrov

    (Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702, USA)

  • Joseph Sodroski

    (Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA)

  • Richard Wyatt

    (Vaccine Research Center, and,)

  • Gary J. Nabel

    (Vaccine Research Center, and,)

  • Peter D. Kwong

    (Vaccine Research Center, and,)

Abstract

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 Å 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.

Suggested Citation

  • Tongqing Zhou & Ling Xu & Barna Dey & Ann J. Hessell & Donald Van Ryk & Shi-Hua Xiang & Xinzhen Yang & Mei-Yun Zhang & Michael B. Zwick & James Arthos & Dennis R. Burton & Dimiter S. Dimitrov & Joseph, 2007. "Structural definition of a conserved neutralization epitope on HIV-1 gp120," Nature, Nature, vol. 445(7129), pages 732-737, February.
    • Handle: RePEc:nat:nature:v:445:y:2007:i:7129:d:10.1038_nature05580
    DOI: 10.1038/nature05580
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    Cited by:

    1. Wen-Han Yu & Peng Zhao & Monia Draghi & Claudia Arevalo & Christina B Karsten & Todd J Suscovich & Bronwyn Gunn & Hendrik Streeck & Abraham L Brass & Michael Tiemeyer & Michael Seaman & John R Mascola, 2018. "Exploiting glycan topography for computational design of Env glycoprotein antigenicity," PLOS Computational Biology, Public Library of Science, vol. 14(4), pages 1-28, April.
    2. Javier Guenaga & Richard T Wyatt, 2012. "Structure-guided Alterations of the gp41-directed HIV-1 Broadly Neutralizing Antibody 2F5 Reveal New Properties Regarding its Neutralizing Function," PLOS Pathogens, Public Library of Science, vol. 8(7), pages 1-15, July.
    3. Zhi Yang & Kim-Marie A. Dam & Michael D. Bridges & Magnus A. G. Hoffmann & Andrew T. DeLaitsch & Harry B. Gristick & Amelia Escolano & Rajeev Gautam & Malcolm A. Martin & Michel C. Nussenzweig & Wayne, 2022. "Neutralizing antibodies induced in immunized macaques recognize the CD4-binding site on an occluded-open HIV-1 envelope trimer," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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