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.

authors

White JF,Grodnitzky J,Louis JM,Trinh LB,Shiloach J,Gutierrez J,Northup JK,Grisshammer R

doi

10.1073/pnas.0705312104

subject

Has Abstract

pub_date

2007-07-17 00:00:00

pages

12199-204

issue

29

eissn

0027-8424

issn

1091-6490

pii

0705312104

journal_volume

104

pub_type

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