Electrostatic interactions and binding orientation of HIV-1 matrix studied by neutron reflectivity.
Biophys J
; 99(8): 2516-24, 2010 Oct 20.
Article
en En
| MEDLINE
| ID: mdl-20959092
ABSTRACT
The N-terminal matrix (MA) domain of the HIV-1 Gag protein is responsible for binding to the plasma membrane of host cells during viral assembly. The putative membrane-binding interface of MA was previously mapped by means of mutagenesis and analysis of its trimeric crystal structure. However, the orientation of MA on membranes has not been directly determined by experimental measurements. We present neutron reflectivity measurements that resolve the one-dimensional scattering length density profile of MA bound to a biomimetic of the native viral membrane. A molecular refinement procedure was developed using atomic structures of MA to determine the orientation of the protein on the membrane. The orientation defines a lipid-binding interface consistent with previous mutagenesis results. The MA protein maintains this orientation without the presence of a myristate group, driven only by electrostatic interactions. Furthermore, MA is found to penetrate the membrane headgroup region peripherally such that only the side chains of specific Lys and Arg residues interact with the surface. The results suggest that electrostatic interactions are sufficient to favorably orient MA on viral membrane mimics. The spatial determination of the membrane-bound protein demonstrates the ability of neutron reflectivity to discern orientation and penetration under physiologically relevant conditions.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
VIH-1
/
Difracción de Neutrones
/
Productos del Gen gag del Virus de la Inmunodeficiencia Humana
/
Electricidad Estática
Tipo de estudio:
Health_economic_evaluation
Idioma:
En
Revista:
Biophys J
Año:
2010
Tipo del documento:
Article
País de afiliación:
Estados Unidos