Structural basis for llama nanobody recognition and neutralization of HIV-1 at the CD4-binding site.
Structure
; 30(6): 862-875.e4, 2022 06 02.
Article
em En
| MEDLINE
| ID: mdl-35413243
ABSTRACT
Nanobodies can achieve remarkable neutralization of genetically diverse pathogens, including HIV-1. To gain insight into their recognition, we determined crystal structures of four llama nanobodies (J3, A12, C8, and D7), all of which targeted the CD4-binding site, in complex with the HIV-1 envelope (Env) gp120 core, and determined a cryoelectron microscopy (cryo-EM) structure of J3 with the Env trimer. Crystal and cryo-EM structures of J3 complexes revealed this nanobody to mimic binding to the prefusion-closed trimer for the primary site of CD4 recognition as well as a secondary quaternary site. In contrast, crystal structures of A12, C8, and D7 with gp120 revealed epitopes that included portions of the gp120 inner domain, inaccessible on the prefusion-closed trimer. Overall, these structures explain the broad and potent neutralization of J3 and limited neutralization of A12, C8, and D7, which utilized binding modes incompatible with the neutralization-targeted prefusion-closed conformation of Env.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Camelídeos Americanos
/
HIV-1
/
Anticorpos de Domínio Único
Limite:
Animals
Idioma:
En
Revista:
Structure
Assunto da revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
/
BIOTECNOLOGIA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos