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Structure of a cleavage-independent HIV Env recapitulates the glycoprotein architecture of the native cleaved trimer

Author

Listed:
  • Anita Sarkar

    (IAVI Neutralizing Antibody Center, The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute)

  • Shridhar Bale

    (The Scripps Research Institute)

  • Anna-Janina Behrens

    (University of Oxford)

  • Sonu Kumar

    (IAVI Neutralizing Antibody Center, The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute)

  • Shailendra Kumar Sharma

    (IAVI Neutralizing Antibody Center, The Scripps Research Institute
    The Scripps Research Institute)

  • Natalia de Val

    (IAVI Neutralizing Antibody Center, The Scripps Research Institute
    The Scripps Research Institute)

  • Jesper Pallesen

    (The Scripps Research Institute
    The Scripps Research Institute)

  • Adriana Irimia

    (IAVI Neutralizing Antibody Center, The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute)

  • Devan C. Diwanji

    (The Scripps Research Institute)

  • Robyn L. Stanfield

    (IAVI Neutralizing Antibody Center, The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute)

  • Andrew B. Ward

    (IAVI Neutralizing Antibody Center, The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute)

  • Max Crispin

    (The Scripps Research Institute
    University of Oxford
    Centre for Biological Sciences and Institute for Life Sciences, University of Southampton)

  • Richard T. Wyatt

    (IAVI Neutralizing Antibody Center, The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute)

  • Ian A. Wilson

    (IAVI Neutralizing Antibody Center, The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute)

Abstract

Furin cleavage of the HIV envelope glycoprotein is an essential step for cell entry that enables formation of well-folded, native-like glycosylated trimers, releases constraints on the fusion peptide, and limits enzymatic processing of the N-glycan shield. Here, we show that a cleavage-independent, stabilized, soluble Env trimer mimic (BG505 NFL.664) exhibits a “closed-form”, native-like, prefusion conformation akin to furin-cleaved Env trimers. The crystal structure of BG505 NFL.664 at 3.39 Å resolution with two potent bNAbs also identifies the full epitopes of PGV19 and PGT122 that target the receptor binding site and N332 supersite, respectively. Quantitative site-specific analysis of the glycan shield reveals that native-like glycan processing is maintained despite furin-independent maturation in the secretory pathway. Thus, cleavage-independent NFL Env trimers exhibit quaternary protein and carbohydrate structures similar to the native viral spike that further validate their potential as vaccine immunogen candidates.

Suggested Citation

  • Anita Sarkar & Shridhar Bale & Anna-Janina Behrens & Sonu Kumar & Shailendra Kumar Sharma & Natalia de Val & Jesper Pallesen & Adriana Irimia & Devan C. Diwanji & Robyn L. Stanfield & Andrew B. Ward &, 2018. "Structure of a cleavage-independent HIV Env recapitulates the glycoprotein architecture of the native cleaved trimer," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04272-y
    DOI: 10.1038/s41467-018-04272-y
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