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Crystal structure, conformational fixation and entry-related interactions of mature ligand-free HIV-1 Env.
Kwon, Young Do; Pancera, Marie; Acharya, Priyamvada; Georgiev, Ivelin S; Crooks, Emma T; Gorman, Jason; Joyce, M Gordon; Guttman, Miklos; Ma, Xiaochu; Narpala, Sandeep; Soto, Cinque; Terry, Daniel S; Yang, Yongping; Zhou, Tongqing; Ahlsen, Goran; Bailer, Robert T; Chambers, Michael; Chuang, Gwo-Yu; Doria-Rose, Nicole A; Druz, Aliaksandr; Hallen, Mark A; Harned, Adam; Kirys, Tatsiana; Louder, Mark K; O'Dell, Sijy; Ofek, Gilad; Osawa, Keiko; Prabhakaran, Madhu; Sastry, Mallika; Stewart-Jones, Guillaume B E; Stuckey, Jonathan; Thomas, Paul V; Tittley, Tishina; Williams, Constance; Zhang, Baoshan; Zhao, Hong; Zhou, Zhou; Donald, Bruce R; Lee, Lawrence K; Zolla-Pazner, Susan; Baxa, Ulrich; Schön, Arne; Freire, Ernesto; Shapiro, Lawrence; Lee, Kelly K; Arthos, James; Munro, James B; Blanchard, Scott C; Mothes, Walther; Binley, James M.
Afiliação
  • Kwon YD; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Pancera M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Acharya P; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Georgiev IS; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Crooks ET; San Diego Biomedical Research Institute, San Diego, California, USA.
  • Gorman J; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Joyce MG; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Guttman M; Department of Medicinal Chemistry, University of Washington, Seattle, Washington, USA.
  • Ma X; Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut, USA.
  • Narpala S; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Soto C; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Terry DS; Department of Physiology and Biophysics, Weill Cornell Medical College of Cornell University, New York, New York, USA.
  • Yang Y; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Zhou T; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Ahlsen G; 1] Department of Biochemistry &Molecular Biophysics, Columbia University, New York, New York, USA. [2] Department of Systems Biology, Columbia University, New York, New York, USA.
  • Bailer RT; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Chambers M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Chuang GY; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Doria-Rose NA; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Druz A; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Hallen MA; 1] Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. [2] Department of Biochemistry, Duke University Medical Center, Durham, North Carolina, USA.
  • Harned A; Electron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
  • Kirys T; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Louder MK; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • O'Dell S; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Ofek G; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Osawa K; San Diego Biomedical Research Institute, San Diego, California, USA.
  • Prabhakaran M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Sastry M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Stewart-Jones GB; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Stuckey J; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Thomas PV; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Tittley T; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Williams C; New York University School of Medicine, New York, New York, USA.
  • Zhang B; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Zhao H; Department of Physiology and Biophysics, Weill Cornell Medical College of Cornell University, New York, New York, USA.
  • Zhou Z; Department of Physiology and Biophysics, Weill Cornell Medical College of Cornell University, New York, New York, USA.
  • Donald BR; 1] Department of Biochemistry, Duke University Medical Center, Durham, North Carolina, USA. [2] Department of Chemistry, Duke University, Durham, North Carolina, USA. [3] Department of Computer Science, Duke University, Durham, North Carolina, USA.
  • Lee LK; Structural and Computational Biology Division, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia.
  • Zolla-Pazner S; 1] New York University School of Medicine, New York, New York, USA. [2] New York Veterans Affairs Harbor Healthcare System, New York, New York, USA.
  • Baxa U; Electron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
  • Schön A; Department of Biology, Johns Hopkins University, Baltimore, Maryland, USA.
  • Freire E; Department of Biology, Johns Hopkins University, Baltimore, Maryland, USA.
  • Shapiro L; 1] Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. [2] Department of Biochemistry &Molecular Biophysics, Columbia University, New York, New York, USA.
  • Lee KK; Department of Medicinal Chemistry, University of Washington, Seattle, Washington, USA.
  • Arthos J; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Munro JB; 1] Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut, USA. [2] Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, USA.
  • Blanchard SC; Department of Physiology and Biophysics, Weill Cornell Medical College of Cornell University, New York, New York, USA.
  • Mothes W; Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut, USA.
  • Binley JM; San Diego Biomedical Research Institute, San Diego, California, USA.
Nat Struct Mol Biol ; 22(7): 522-31, 2015 Jul.
Article em En | MEDLINE | ID: mdl-26098315
ABSTRACT
As the sole viral antigen on the HIV-1-virion surface, trimeric Env is a focus of vaccine efforts. Here we present the structure of the ligand-free HIV-1-Env trimer, fix its conformation and determine its receptor interactions. Epitope analyses revealed trimeric ligand-free Env to be structurally compatible with broadly neutralizing antibodies but not poorly neutralizing ones. We coupled these compatibility considerations with binding antigenicity to engineer conformationally fixed Envs, including a 201C 433C (DS) variant specifically recognized by broadly neutralizing antibodies. DS-Env retained nanomolar affinity for the CD4 receptor, with which it formed an asymmetric intermediate a closed trimer bound by a single CD4 without the typical antigenic hallmarks of CD4 induction. Antigenicity-guided structural design can thus be used both to delineate mechanism and to fix conformation, with DS-Env trimers in virus-like-particle and soluble formats providing a new generation of vaccine antigens.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Anticorpos Anti-HIV / Infecções por HIV / HIV-1 / Produtos do Gene env do Vírus da Imunodeficiência Humana / Anticorpos Neutralizantes Limite: Humans Idioma: En Ano de publicação: 2015 Tipo de documento: Article
Texto completo
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XML
PubMed Links
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Anticorpos Anti-HIV / Infecções por HIV / HIV-1 / Produtos do Gene env do Vírus da Imunodeficiência Humana / Anticorpos Neutralizantes Limite: Humans Idioma: En Ano de publicação: 2015 Tipo de documento: Article