Library Portal | UWC Portal
    • Login
    Contact Us | Quick Submission Guide | About Us | FAQs | Login
    View Item 
    •   Repository Home
    • Faculty of Natural Sciences
    • South African National Bioinformatics Institute (SANBI)
    • Research Articles (SANBI)
    • View Item
    •   Repository Home
    • Faculty of Natural Sciences
    • South African National Bioinformatics Institute (SANBI)
    • Research Articles (SANBI)
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Structural rearrangements maintain the Glycan Shield of an HIV-1 envelope trimer after the loss of a glycan

    Thumbnail
    View/Open
    Ferreira_Structural-rearrangements_2018.pdf (4.389Mb)
    Date
    2018
    Author
    Ferreira, Roux-Cil
    Grant, Oliver C.
    Moyo, Thandeka
    Dorfman, Jeffrey R.
    Woods, Robert J.
    Travers, Simon A.
    Wood, Natasha T.
    Metadata
    Show full item record
    Abstract
    The HIV-1 envelope (Env) glycoprotein is the primary target of the humoral immune response and a critical vaccine candidate. However, Env is densely glycosylated and thereby substantially protected from neutralisation. Importantly, glycan N301 shields V3 loop and CD4 binding site epitopes from neutralising antibodies. Here, we use molecular dynamics techniques to evaluate the structural rearrangements that maintain the protective qualities of the glycan shield after the loss of glycan N301. We examined a naturally occurring subtype C isolate and its N301A mutant; the mutant not only remained protected against neutralising antibodies targeting underlying epitopes, but also exhibited an increased resistance to the VRC01 class of broadly neutralising antibodies. Analysis of this mutant revealed several glycans that were responsible, independently or through synergy, for the neutralisation resistance of the mutant. These data provide detailed insight into the glycan shield’s ability to compensate for the loss of a glycan, as well as the cascade of glycan movements on a protomer, starting at the point mutation, that affects the integrity of an antibody epitope located at the edge of the diminishing effect. These results present key, previously overlooked, considerations for HIV-1 Env glycan research and related vaccine studies.
    URI
    http://dx.doiorg/10.1038/s41598-018-33390-2
    http://hdl.handle.net/10566/4117
    Collections
    • Research Articles (SANBI) [76]

    DSpace 5.5 | Ubuntu 14.04 | Copyright © University of the Western Cape
    Contact Us | Send Feedback
    Theme by 
    @mire NV
     

     

    Browse

    All of RepositoryCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    Statistics

    View Usage Statistics

    DSpace 5.5 | Ubuntu 14.04 | Copyright © University of the Western Cape
    Contact Us | Send Feedback
    Theme by 
    @mire NV