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Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9

Author

Listed:
  • Jason S. McLellan

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • Marie Pancera

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • Chris Carrico

    (University of Washington, Seattle, Washington 98195, USA)

  • Jason Gorman

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • Jean-Philippe Julien

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

  • Reza Khayat

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

  • Robert Louder

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • Robert Pejchal

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

  • Mallika Sastry

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • Kaifan Dai

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • Sijy O’Dell

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • Nikita Patel

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

  • Syed Shahzad-ul-Hussan

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • Yongping Yang

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • Baoshan Zhang

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • Tongqing Zhou

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • Jiang Zhu

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • Jeffrey C. Boyington

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • Gwo-Yu Chuang

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • Devan Diwanji

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

  • Ivelin Georgiev

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • Young Do Kwon

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • Doyung Lee

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • Mark K. Louder

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • Stephanie Moquin

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • Stephen D. Schmidt

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • Zhi-Yong Yang

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • Mattia Bonsignori

    (The Duke Human Vaccine Institute, Duke University School of Medicine, and Duke University Medical Center, Durham, North Carolina 27710, USA)

  • John A. Crump

    (Duke University Medical Center, Durham, North Carolina 27710, USA
    Kilimanjaro Christian Medical Centre and Kilimanjaro Christian Medical College, Tumaini University)

  • Saidi H. Kapiga

    (Kilimanjaro Reproductive Health Programme)

  • Noel E. Sam

    (Kilimanjaro Christian Medical Centre and Kilimanjaro Christian Medical College, Tumaini University
    Kilimanjaro Reproductive Health Programme)

  • Barton F. Haynes

    (The Duke Human Vaccine Institute, Duke University School of Medicine, and Duke University Medical Center, Durham, North Carolina 27710, USA)

  • Dennis R. Burton

    (The Scripps Research Institute, La Jolla, California 92037, USA
    Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts 02129, USA)

  • Wayne C. Koff

    (International AIDS Vaccine Initiative (IAVI), New York, New York 10004, USA)

  • Laura M. Walker

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

  • Sanjay Phogat

    (International AIDS Vaccine Initiative (IAVI), New York, New York 10004, USA)

  • Richard Wyatt

    (IAVI Neutralizing Antibody Center at TSRI, The Scripps Research Institute, La Jolla, California 92037, USA)

  • Jared Orwenyo

    (University of Maryland School of Medicine, Baltimore, Maryland 21201, USA)

  • Lai-Xi Wang

    (University of Maryland School of Medicine, Baltimore, Maryland 21201, USA)

  • James Arthos

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

  • Carole A. Bewley

    (Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • John R. Mascola

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • Gary J. Nabel

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • William R. Schief

    (University of Washington, Seattle, Washington 98195, USA
    The Scripps Research Institute, La Jolla, California 92037, USA)

  • Andrew B. Ward

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

  • Ian A. Wilson

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

  • Peter D. Kwong

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA)

Abstract

Variable regions 1 and 2 (V1/V2) of human immunodeficiency virus-1 (HIV-1) gp120 envelope glycoprotein are critical for viral evasion of antibody neutralization, and are themselves protected by extraordinary sequence diversity and N-linked glycosylation. Human antibodies such as PG9 nonetheless engage V1/V2 and neutralize 80% of HIV-1 isolates. Here we report the structure of V1/V2 in complex with PG9. V1/V2 forms a four-stranded β-sheet domain, in which sequence diversity and glycosylation are largely segregated to strand-connecting loops. PG9 recognition involves electrostatic, sequence-independent and glycan interactions: the latter account for over half the interactive surface but are of sufficiently weak affinity to avoid autoreactivity. The structures of V1/V2-directed antibodies CH04 and PGT145 indicate that they share a common mode of glycan penetration by extended anionic loops. In addition to structurally defining V1/V2, the results thus identify a paradigm of antibody recognition for highly glycosylated antigens, which—with PG9—involves a site of vulnerability comprising just two glycans and a strand.

Suggested Citation

  • Jason S. McLellan & Marie Pancera & Chris Carrico & Jason Gorman & Jean-Philippe Julien & Reza Khayat & Robert Louder & Robert Pejchal & Mallika Sastry & Kaifan Dai & Sijy O’Dell & Nikita Patel & Syed, 2011. "Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9," Nature, Nature, vol. 480(7377), pages 336-343, December.
    • Handle: RePEc:nat:nature:v:480:y:2011:i:7377:d:10.1038_nature10696
    DOI: 10.1038/nature10696
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    Cited by:

    1. Svenja Weiss & Vincenza Itri & Ruimin Pan & Xunqing Jiang & Christina C. Luo & Lynn Morris & Delphine C. Malherbe & Philip Barnette & Jeff Alexander & Xiang-Peng Kong & Nancy L. Haigwood & Ann J. Hess, 2022. "Differential V2-directed antibody responses in non-human primates infected with SHIVs or immunized with diverse HIV vaccines," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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