Substrate-induced changes in the dynamics of rhodopsin kinase (G protein-coupled receptor kinase 1).
Biochemistry
; 51(16): 3404-11, 2012 Apr 24.
Article
en En
| MEDLINE
| ID: mdl-22480180
ABSTRACT
G protein-coupled receptor (GPCR) kinases (GRKs) instigate the desensitization of activated GPCRs via phosphorylation that promotes interaction with arrestins, thereby preventing the interaction of GPCRs with heterotrimeric G proteins. A current proposed model of GRK1 activation involves the binding of activated rhodopsin (Rho*) to the N-terminal region of GRK1. Perhaps concomitantly, this N-terminal region also stabilizes a closed, active conformation of the kinase domain. To further probe this model, we mapped changes in the backbone flexibility of GRK1 as it binds to its two substrates, adenosine triphosphate (Mg(2+)·ATP) and Rho*. We found that the conformational flexibility of GRK1 was reduced in the presence of either Mg(2+)·ATP or Rho*, with Mg(2+)·ATP having the greatest effect. In a truncated form of GRK1 lacking the N-terminal region (ΔN-GRK1), peptides that directly interact with ATP were not as dramatically stabilized by adding Mg(2+)·ATP, and dynamics were greater in the interface between the large lobe of the kinase domain and the regulator of the G protein signaling homology domain. In the presence of Mg(2+)·ATP, the influence of Rho* versus Rho on GRK1 dynamics was negligible.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Quinasa 1 del Receptor Acoplado a Proteína-G
Límite:
Animals
Idioma:
En
Revista:
Biochemistry
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos