title: Conformational dynamics of single HIV-1 envelope trimers on the surface of native virions.
abstract: The HIV-1 envelope (Env) mediates viral entry into host cells. To enable the direct imaging of conformational dynamics within Env, we introduced fluorophores into variable regions of the glycoprotein gp120 subunit and measured single-molecule fluorescence resonance energy transfer within the context of native trimers on the surface of HIV-1 virions. Our observations revealed unliganded HIV-1 Env to be intrinsically dynamic, transitioning between three distinct prefusion conformations, whose relative occupancies were remodeled by receptor CD4 and antibody binding. The distinct properties of neutralization-sensitive and neutralization-resistant HIV-1 isolates support a dynamics-based mechanism of immune evasion and ligand recognition.
authors.affiliation: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA. walther.mothes@yale.edu scb2005@med.cornell.edu james.munro@tufts.edu.
authors.forename: James B
authors.initials: JB
authors.lastname: Munro
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Gorman
authors.affiliation: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA.
authors.forename: Xiaochu
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Physiology and Biophysics, Weill Cornell Medical College of Cornell University, New York, NY 10021, USA.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: James
authors.initials: J
authors.lastname: Arthos
authors.affiliation: Department of Immunology and Microbial Science, and IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02129, USA.
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Burton
authors.affiliation: International AIDS Vaccine Initiative (IAVI), New York, NY 10004, USA.
authors.forename: Wayne C
authors.initials: WC
authors.lastname: Koff
authors.affiliation: Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Joel R
authors.initials: JR
authors.lastname: Courter
authors.affiliation: Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Amos B
authors.initials: AB
authors.lastname: Smith
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Kwong
authors.affiliation: Department of Physiology and Biophysics, Weill Cornell Medical College of Cornell University, New York, NY 10021, USA. walther.mothes@yale.edu scb2005@med.cornell.edu james.munro@tufts.edu.
authors.forename: Scott C
authors.initials: SC
authors.lastname: Blanchard
authors.affiliation: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA. walther.mothes@yale.edu scb2005@med.cornell.edu james.munro@tufts.edu.
authors.forename: Walther
authors.initials: W
authors.lastname: Mothes
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D031541:Fluorescence Resonance Energy Transfer / Q000379:methods; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000276:immunology; D015497:HIV-1 / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D057131:Immune Evasion; D008024:Ligands; D008956:Models, Chemical; D057054:Molecular Imaging / Q000379:methods; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D014771:Virion / Q000737:chemistry* / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D008024:Ligands