Identification of the HIV-1 Vif and Human APOBEC3G Protein Interface.
Cell Rep
; 13(9): 1789-99, 2015 Dec 01.
Article
en En
| MEDLINE
| ID: mdl-26628364
ABSTRACT
Human cells express natural antiviral proteins, such as APOBEC3G (A3G), that potently restrict HIV replication. As a counter-defense, HIV encodes the accessory protein Vif, which binds A3G and mediates its proteasomal degradation. Our structural knowledge on how Vif and A3G interact is limited, because a co-structure is not available. We identified specific points of contact between Vif and A3G by using functional assays with full-length A3G, patient-derived Vif variants, and HIV forced evolution. These anchor points were used to model and validate the Vif-A3G interface. The resultant co-structure model shows that the negatively charged ß4-α4 A3G loop, which contains primate-specific variation, is the core Vif binding site and forms extensive interactions with a positively charged pocket in HIV Vif. Our data present a functional map of this viral-host interface and open avenues for targeted approaches to block HIV replication by obstructing the Vif-A3G interaction.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
VIH-1
/
Productos del Gen vif del Virus de la Inmunodeficiencia Humana
/
Desaminasa APOBEC-3G
Tipo de estudio:
Diagnostic_studies
Límite:
Humans
Idioma:
En
Revista:
Cell Rep
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos