IDEAS home Printed from https://ideas.repec.org/a/plo/pone00/0037530.html
   My bibliography  Save this article

Structural Dynamics of HIV-1 Envelope Gp120 Outer Domain with V3 Loop

Author

Listed:
  • Masaru Yokoyama
  • Satoshi Naganawa
  • Kazuhisa Yoshimura
  • Shuzo Matsushita
  • Hironori Sato

Abstract

Background: The net charge of the hypervariable V3 loop on the HIV-1 envelope gp120 outer domain plays a key role in modulating viral phenotype. However, the molecular mechanisms underlying the modulation remain poorly understood. Methodology/Principal Findings: By combining computational and experimental approaches, we examined how V3 net charge could influence the phenotype of the gp120 interaction surface. Molecular dynamics simulations of the identical gp120 outer domain, carrying a V3 loop with net charge of +3 or +7, showed that the V3 change alone could induce global changes in fluctuation and conformation of the loops involved in binding to CD4, coreceptor and antibodies. A neutralization study using the V3 recombinant HIV-1 infectious clones showed that the virus carrying the gp120 with +3 V3, but not with +7 V3, was resistant to neutralization by anti-CD4 binding site monoclonal antibodies. An information entropy study shows that otherwise variable surface of the gp120 outer domain, such as V3 and a region around the CD4 binding loop, are less heterogeneous in the gp120 subpopulation with +3 V3. Conclusions/Significance: These results suggest that the HIV-1 gp120 V3 loop acts as an electrostatic modulator that influences the global structure and diversity of the interaction surface of the gp120 outer domain. Our findings will provide a novel structural basis to understand how HIV-1 adjusts relative replication fitness by V3 mutations.

Suggested Citation

  • Masaru Yokoyama & Satoshi Naganawa & Kazuhisa Yoshimura & Shuzo Matsushita & Hironori Sato, 2012. "Structural Dynamics of HIV-1 Envelope Gp120 Outer Domain with V3 Loop," PLOS ONE, Public Library of Science, vol. 7(5), pages 1-9, May.
  • Handle: RePEc:plo:pone00:0037530
    DOI: 10.1371/journal.pone.0037530
    as

    Download full text from publisher

    File URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0037530
    Download Restriction: no

    File URL: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0037530&type=printable
    Download Restriction: no

    File URL: https://libkey.io/10.1371/journal.pone.0037530?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. 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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. 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.
    2. 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.
    3. 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.
    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. 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.
    6. 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.
    7. 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.
    8. 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.
    9. 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.
    10. 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.
    11. 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.
    12. 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.
    13. Avradip Chatterjee & Brad Gallent & Madhusudhanarao Katiki & Chen Qian & Matthew R. Harter & Steve Silletti & Elizabeth A. Komives & Michael R. Freeman & Ramachandran Murali, 2024. "The homeodomain regulates stable DNA binding of prostate cancer target ONECUT2," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    14. 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.
    15. 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.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:plo:pone00:0037530. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: plosone (email available below). General contact details of provider: https://journals.plos.org/plosone/ .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.