Dimerization of the class A G protein-coupled neurotensin receptor NTS1 alters G protein interaction.
Proc Natl Acad Sci U S A
; 104(29): 12199-204, 2007 Jul 17.
Article
em En
| MEDLINE
| ID: mdl-17620610
ABSTRACT
G protein-coupled receptors (GPCRs) have been found as monomers but also as dimers or higher-order oligomers in cells. The relevance of the monomeric or dimeric receptor state for G protein activation is currently under debate for class A rhodopsin-like GPCRs. Clarification of this issue requires the availability of well defined receptor preparations as monomers or dimers and an assessment of their ligand-binding and G protein-coupling properties. We show by pharmacological and hydrodynamic experiments that purified neurotensin receptor NTS1, a class A GPCR, dimerizes in detergent solution in a concentration-dependent manner, with an apparent affinity in the low nanomolar range. At low receptor concentrations, NTS1 binds the agonist neurotensin with a Hill slope of approximately 1; at higher receptor concentrations, neurotensin binding displays positive cooperativity with a Hill slope of approximately 2. NTS1 monomers activate G alpha q beta(1)gamma(2), whereas receptor dimers catalyze nucleotide exchange with lower affinity. Our results demonstrate that NTS1 dimerization per se is not a prerequisite for G protein activation.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Receptores de Neurotensina
/
Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Estados Unidos