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Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody

Author

Listed:
  • Peter D. Kwong

    (Columbia University)

  • Richard Wyatt

    (Dana-Farber Cancer Institute, Harvard Medical School, Harvard School of Public Health)

  • James Robinson

    (Tulane University Medical Center)

  • Raymond W. Sweet

    (SmithKline Beecham Pharmaceuticals)

  • Joseph Sodroski

    (Dana-Farber Cancer Institute, Harvard Medical School, Harvard School of Public Health
    Harvard School of Public Health)

  • Wayne A. Hendrickson

    (Columbia University
    Howard Hughes Medical Institute, Columbia University)

Abstract

The entry of human immunodeficiency virus (HIV) into cells requires the sequential interaction of the viral exterior envelope glycoprotein, gp120, with the CD4 glycoprotein and a chemokine receptor on the cell surface. These interactions initiate a fusion of the viral and cellular membranes. Although gpl20 can elicit virus-neutralizing antibodies, HIV eludes the immune system. We have solved the X-ray crystal structure at 2.5 Å resolution of an HIV-1 gp120 core complexed with a two-domain fragment of human CD4 and an antigen-binding fragment of a neutralizing antibody that blocks chemokine-receptor binding. The structure reveals a cavity-laden CD4–gp120 interface, a conserved binding site for the chemokine receptor, evidence for a conformational change upon CD4 binding, the nature of a CD4-induced antibody epitope, and specific mechanisms for immune evasion. Our results provide a framework for understanding the complex biology of HIV entry into cells and should guide efforts to intervene.

Suggested Citation

  • Peter D. Kwong & Richard Wyatt & James Robinson & Raymond W. Sweet & Joseph Sodroski & Wayne A. Hendrickson, 1998. "Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody," Nature, Nature, vol. 393(6686), pages 648-659, June.
    • Handle: RePEc:nat:nature:v:393:y:1998:i:6686:d:10.1038_31405
    DOI: 10.1038/31405
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    Cited by:

    1. Terrence M Dobrowsky & Brian R Daniels & Robert F Siliciano & Sean X Sun & Denis Wirtz, 2010. "Organization of Cellular Receptors into a Nanoscale Junction during HIV-1 Adhesion," PLOS Computational Biology, Public Library of Science, vol. 6(7), pages 1-14, July.
    2. Hao Zhang & Peng Wang & Nikitas Papangelopoulos & Ying Xu & Alessandro Sette & Philip E Bourne & Ole Lund & Julia Ponomarenko & Morten Nielsen & Bjoern Peters, 2010. "Limitations of Ab Initio Predictions of Peptide Binding to MHC Class II Molecules," PLOS ONE, Public Library of Science, vol. 5(2), pages 1-10, February.
    3. Hongjun Bai & Eric Lewitus & Yifan Li & Paul V. Thomas & Michelle Zemil & Mélanie Merbah & Caroline E. Peterson & Thujitha Thuraisamy & Phyllis A. Rees & Agnes Hajduczki & Vincent Dussupt & Bonnie Sli, 2024. "Contemporary HIV-1 consensus Env with AI-assisted redesigned hypervariable loops promote antibody binding," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    4. 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.
    5. Aliana López de Victoria & Phanourios Tamamis & Chris A Kieslich & Dimitrios Morikis, 2012. "Insights into the Structure, Correlated Motions, and Electrostatic Properties of Two HIV-1 gp120 V3 Loops," PLOS ONE, Public Library of Science, vol. 7(11), pages 1-15, November.
    6. Shixia Wang & Kun-Wei Chan & Danlan Wei & Xiuwen Ma & Shuying Liu & Guangnan Hu & Saeyoung Park & Ruimin Pan & Ying Gu & Alexandra F. Nazzari & Adam S. Olia & Kai Xu & Bob C. Lin & Mark K. Louder & Kr, 2024. "Human CD4-binding site antibody elicited by polyvalent DNA prime-protein boost vaccine neutralizes cross-clade tier-2-HIV strains," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    7. Ignacio Fernández & Lasse Toftdal Dynesen & Youna Coquin & Riccardo Pederzoli & Delphine Brun & Ahmed Haouz & Antoine Gessain & Félix A. Rey & Florence Buseyne & Marija Backovic, 2023. "The crystal structure of a simian Foamy Virus receptor binding domain provides clues about entry into host cells," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    8. Jérémie Prévost & Yaozong Chen & Fei Zhou & William D. Tolbert & Romain Gasser & Halima Medjahed & Manon Nayrac & Dung N. Nguyen & Suneetha Gottumukkala & Ann J. Hessell & Venigalla B. Rao & Edwin Poz, 2023. "Structure-function analyses reveal key molecular determinants of HIV-1 CRF01_AE resistance to the entry inhibitor temsavir," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    9. Carsten Magnus & Roland R Regoes, 2010. "Estimating the Stoichiometry of HIV Neutralization," PLOS Computational Biology, Public Library of Science, vol. 6(3), pages 1-11, March.
    10. Yang Yang & DeGruttola Victor, 2012. "Resampling-based Methods in Single and Multiple Testing for Equality of Covariance/Correlation Matrices," The International Journal of Biostatistics, De Gruyter, vol. 8(1), pages 1-32, June.
    11. Lingli Kong & Jianfang Liu & Meng Zhang & Zhuoyang Lu & Han Xue & Amy Ren & Jiankang Liu & Jinping Li & Wai Li Ling & Gang Ren, 2023. "Facile hermetic TEM grid preparation for molecular imaging of hydrated biological samples at room temperature," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    12. Jun Niu & Qi Wang & Wenwen Zhao & Bing Meng & Youwei Xu & Xianfang Zhang & Yi Feng & Qilian Qi & Yanling Hao & Xuan Zhang & Ying Liu & Jiangchao Xiang & Yiming Shao & Bei Yang, 2023. "Structures and immune recognition of Env trimers from two Asia prevalent HIV-1 CRFs," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    13. Yanay Ofran & Burkhard Rost, 2007. "Protein–Protein Interaction Hotspots Carved into Sequences," PLOS Computational Biology, Public Library of Science, vol. 3(7), pages 1-8, July.
    14. Linjing Zhu & Bilian Huang & Xiangyao Wang & Fengfeng Ni & Mingjun Ao & Ruoke Wang & Bin Zheng & Chen Chen & Jing Xue & Lin Zhu & Chenbo Yang & Lingen Shi & Shengya Geng & Jiaqian Hu & Mengshi Yang & , 2024. "Highly potent and broadly neutralizing anti-CD4 trimeric nanobodies inhibit HIV-1 infection by inducing CD4 conformational alteration," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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