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Subnanometer structures of HIV-1 envelope trimers on aldrithiol-2-inactivated virus particles

  1. Author:
    Li, Ze
    Li, Wenwei
    Lu, Maolin
    Bess,Julian
    Chao, Cara W.
    Gorman, Jason
    Terry, Daniel S.
    Zhang, Baoshan
    Zhou, Tongqing
    Blanchard, Scott C.
    Kwong, Peter D.
    Lifson, Jeffrey D.
    Mothes, Walther
    Liu, Jun

  2. Author Address

    Yale Univ, Sch Med, Dept Microbial Pathogenesis, 333 Cedar St, New Haven, CT 06520 USA.Yale Univ, Microbial Sci Inst, West Haven, CT 06520 USA.Fudan Univ, Shanghai Med Coll, Shanghai Canc Ctr, Inst Biomed Sci, Shanghai, Peoples R China.Frederick Natl Lab Canc Res, AIDS & Canc Virus Program, Frederick, MD USA.NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.St Jude Childrens Res Hosp, Dept Struct Biol, 332 N Lauderdale St, Memphis, TN 38105 USA.
    1. Year: 2020
    2. Date: Jun 29
    3. Epub Date: 2020 06 29
  2. Journal: Nature structural & molecular biology
  3. NATURE PUBLISHING GROUP,
  5. Type of Article: Article
  6. ISSN: 1545-9993
  1. Abstract:

    The HIV-1 envelope glycoprotein (Env) trimer, composed of gp120 and gp41 subunits, mediates viral entry into cells. Recombinant Env trimers have been studied structurally, but characterization of Env embedded in intact virus membranes has been limited to low resolution. Here, we deploy cryo-electron tomography and subtomogram averaging to determine the structures of Env trimers on aldrithiol-2 (AT-2)-inactivated virions in ligand-free, antibody-bound and CD4-bound forms at subnanometer resolution. Tomographic reconstructions document molecular features consistent with high-resolution structures of engineered soluble and detergent-solubilized Env trimers. One of three conformational states previously predicted by smFRET was not observed by cryo-ET, potentially owing to AT-2 inactivation. We did observe Env trimers to open in situ in response to CD4 binding, with an outward movement of gp120-variable loops and an extension of a critical gp41 helix. Overall features of Env trimer embedded in AT-2-treated virions appear well-represented by current engineered trimers.

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External Sources

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  2. DOI: 10.1038/s41594-020-0452-2
  3. PMID: 32601441
  4. View record in Web of Science®
  5. WOS: 000544151200001

Library Notes

  1. Fiscal Year: FY2019-2020
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