Imaging G protein-coupled receptors while quantifying their ligand-binding free-energy landscape.
Nat Methods
; 12(9): 845-851, 2015 Sep.
Article
en En
| MEDLINE
| ID: mdl-26167642
ABSTRACT
Imaging native membrane receptors and testing how they interact with ligands is of fundamental interest in the life sciences but has proven remarkably difficult to accomplish. Here, we introduce an approach that uses force-distance curve-based atomic force microscopy to simultaneously image single native G protein-coupled receptors in membranes and quantify their dynamic binding strength to native and synthetic ligands. We measured kinetic and thermodynamic parameters for individual protease-activated receptor-1 (PAR1) molecules in the absence and presence of antagonists, and these measurements enabled us to describe PAR1's ligand-binding free-energy landscape with high accuracy. Our nanoscopic method opens an avenue to directly image and characterize ligand binding of native membrane receptors.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Microscopía de Fuerza Atómica
/
Receptor PAR-1
/
Imagen Molecular
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Membrana Dobles de Lípidos
/
Modelos Químicos
Límite:
Humans
Idioma:
En
Revista:
Nat Methods
Asunto de la revista:
TECNICAS E PROCEDIMENTOS DE LABORATORIO
Año:
2015
Tipo del documento:
Article
País de afiliación:
Suiza