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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 ; McDermott, Adrian B ; Mascola, John R ; Kwong, Peter D

Nature structural & molecular biology, 2015-07, Vol.22 (7), p.522-531 [Periódico revisado por pares]

United States: Nature Publishing Group

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Título:
Crystal structure, conformational fixation and entry-related interactions of mature ligand-free HIV-1 Env
Autor: 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 ; McDermott, Adrian B ; Mascola, John R ; Kwong, Peter D
Assuntos: 60 APPLIED LIFE SCIENCES ; AIDS vaccines ; Antibodies, Neutralizing - immunology ; Antigens ; BASIC BIOLOGICAL SCIENCES ; CD4 Antigens - immunology ; Computational biology and bioinformatics ; Crystal structure ; Crystallography, X-Ray ; env Gene Products, Human Immunodeficiency Virus - chemistry ; env Gene Products, Human Immunodeficiency Virus - immunology ; Epitopes - immunology ; Health aspects ; HEK293 Cells ; HIV ; HIV Antibodies - immunology ; HIV Infections - immunology ; HIV Infections - virology ; HIV-1 - chemistry ; HIV-1 - immunology ; HIV-1 - physiology ; Human immunodeficiency virus ; Human immunodeficiency virus 1 ; Humans ; Immunology ; Models, Molecular ; Molecular biology ; Protein Conformation ; Protein Multimerization ; Vaccines ; Viral antigens ; Viral membrane fusion ; Virus Internalization ; X-ray crystallography
É parte de: Nature structural & molecular biology, 2015-07, Vol.22 (7), p.522-531
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
National Inst. of Health (NIH) (United States)
National Science Foundation (NSF)
Australian Research Council (Australia)
Bill and Melinda Gates Foundation (United States)
USDOE Office of Science (SC), Basic Energy Sciences (BES)
W-31-109-Eng-38; HHSN261200800001E; P01-AI100151; P01-AI104722; R01-AI93278; R21-AI100696; R21-AI112389; R33-AI84714; P01-GM56550; R01-GM78031; R01-GM98859; PO1-HL59725; MCB-1157506; OPP1033102; DP130102219
These authors contributed equally to this work.
Descrição: 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.
Editor: United States: Nature Publishing Group
Idioma: Inglês

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Crystal structure, conformational fixation and entry-related interactions of mature ligand-free HIV-1 Env

United States: Nature Publishing Group

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