Crystal structure, conformational fixation and entry-related interactions of mature ligand-free HIV-1 Env.
Nat Struct Mol Biol
; 22(7): 522-31, 2015 Jul.
Article
de 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.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Anticorps anti-VIH
/
Infections à VIH
/
VIH-1 (Virus de l'Immunodéficience Humaine de type 1)
/
Produits du gène env du virus de l'immunodéficience humaine
/
Anticorps neutralisants
Limites:
Humans
Langue:
En
Journal:
Nat Struct Mol Biol
Sujet du journal:
BIOLOGIA MOLECULAR
Année:
2015
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique