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HIV-1 Envelope and MPER Antibody Structures in Lipid Assemblies.
Rantalainen, Kimmo; Berndsen, Zachary T; Antanasijevic, Aleksandar; Schiffner, Torben; Zhang, Xi; Lee, Wen-Hsin; Torres, Jonathan L; Zhang, Lei; Irimia, Adriana; Copps, Jeffrey; Zhou, Kenneth H; Kwon, Young D; Law, William H; Schramm, Chaim A; Verardi, Raffaello; Krebs, Shelly J; Kwong, Peter D; Doria-Rose, Nicole A; Wilson, Ian A; Zwick, Michael B; Yates, John R; Schief, William R; Ward, Andrew B.
Affiliation
  • Rantalainen K; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA; International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Berndsen ZT; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA; International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Antanasijevic A; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA.
  • Schiffner T; Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Zhang X; Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA, USA.
  • Lee WH; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA; International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Torres JL; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA; International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Zhang L; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Irimia A; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA; International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Development, The Scripps
  • Copps J; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA; International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Zhou KH; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Kwon YD; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Law WH; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Schramm CA; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Verardi R; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Krebs SJ; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Kwong PD; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Doria-Rose NA; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Wilson IA; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA; International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Development, The Scripps
  • Zwick MB; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Yates JR; Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA, USA.
  • Schief WR; International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbiology, The Scripps Research Institute, La
  • Ward AB; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA; International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Development, The Scripps
Cell Rep ; 31(4): 107583, 2020 04 28.
Article in En | MEDLINE | ID: mdl-32348769
ABSTRACT
Structural and functional studies of HIV envelope glycoprotein (Env) as a transmembrane protein have long been complicated by challenges associated with inherent flexibility of the molecule and the membrane-embedded hydrophobic regions. Here, we present approaches for incorporating full-length, wild-type HIV-1 Env, as well as C-terminally truncated and stabilized versions, into lipid assemblies, providing a modular platform for Env structural studies by single particle electron microscopy. We reconstitute a full-length Env clone into a nanodisc, complex it with a membrane-proximal external region (MPER) targeting antibody 10E8, and structurally define the full quaternary epitope of 10E8 consisting of lipid, MPER, and ectodomain contacts. By aligning this and other Env-MPER antibody complex reconstructions with the lipid bilayer, we observe evidence of Env tilting as part of the neutralization mechanism for MPER-targeting antibodies. We also adapt the platform toward vaccine design purposes by introducing stabilizing mutations that allow purification of unliganded Env with a peptidisc scaffold.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: HIV Envelope Protein gp41 / HIV-1 / Lipid Bilayers Limits: Humans Language: En Journal: Cell Rep Year: 2020 Document type: Article Affiliation country:
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: HIV Envelope Protein gp41 / HIV-1 / Lipid Bilayers Limits: Humans Language: En Journal: Cell Rep Year: 2020 Document type: Article Affiliation country: