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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 (1) , 1710. 10.1038/s41467-018-03727-6

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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
Date Type: Publication
Status: Published
Schools: Pharmacy
Publisher: Nature Research
ISSN: 2041-1723
Date of First Compliant Deposit: 3 May 2018
Date of Acceptance: 6 March 2018
Last Modified: 23 Jan 2020 15:48
URI: http://orca.cf.ac.uk/id/eprint/111201

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