Dynamic tuneable G protein-coupled receptor monomer-dimer populations

Dijkman, Patricia M., Castell, Oliver K., Goddard, Alan D., Munoz-Garcia, Juan C., de Graaf, Chris, Wallace, Mark I. and Watts, Anthony (2018) Dynamic tuneable G protein-coupled receptor monomer-dimer populations. Nature Communications, 9. ISSN 2041-1723

[img]
Preview
PDF (Published manuscript) - Published Version
Available under License Creative Commons Attribution.

Download (2MB) | Preview

Abstract

G protein-coupled receptors (GPCRs) are the largest class of membrane receptors, playing a key role in the regulation of processes as varied as neurotransmission and immune response. Evidence for GPCR oligomerisation has been accumulating that challenges the idea that GPCRs function solely as monomeric receptors; however, GPCR oligomerisation remains controversial primarily due to the difficulties in comparing evidence from very different types of structural and dynamic data. Using a combination of single-molecule and ensemble FRET, double electron–electron resonance spectroscopy, and simulations, we show that dimerisation of the GPCR neurotensin receptor 1 is regulated by receptor density and is dynamically tuneable over the physiological range. We propose a “rolling dimer” interface model in which multiple dimer conformations co-exist and interconvert. These findings unite previous seemingly conflicting observations, provide a compelling mechanism for regulating receptor signalling, and act as a guide for future physiological studies.

Item Type: Article
Faculty \ School: Faculty of Science > School of Pharmacy
Related URLs:
Depositing User: Pure Connector
Date Deposited: 01 May 2018 09:30
Last Modified: 13 Oct 2019 00:36
URI: https://ueaeprints.uea.ac.uk/id/eprint/66873
DOI: 10.1038/s41467-018-03727-6

Actions (login required)

View Item View Item