Unknown

Dataset Information

0

Dimerization of the class A G protein-coupled neurotensin receptor NTS1 alters G protein interaction.


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.

SUBMITTER: White JF 

PROVIDER: S-EPMC1913548 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC3294418 | biostudies-literature
| S-EPMC2696590 | biostudies-literature
| S-EPMC2716571 | biostudies-literature
| S-EPMC3369761 | biostudies-literature
| S-EPMC196868 | biostudies-literature
| S-EPMC5274527 | biostudies-literature
| S-EPMC7331637 | biostudies-literature
| S-EPMC4512254 | biostudies-literature
| S-EPMC4597782 | biostudies-literature
| S-EPMC11241240 | biostudies-literature