Dynamic tuneable G protein-coupled receptor monomer-dimer populations

Patricia M. Dijkman, Oliver K. Castell, Alan Goddard, Juan C. Munoz-Garcia, Chris de Graaf, Mark I. Wallace, Anthony Watts

Research output: Contribution to journalArticle

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.
LanguageEnglish
Article number1710
JournalNature Communications
Volume9
Early online date27 Apr 2018
DOIs
Publication statusE-pub ahead of print - 27 Apr 2018

Fingerprint

G-Protein-Coupled Receptors
Dimers
monomers
Monomers
dimers
proteins
Oligomerization
Population
Electron resonance
Electrons
Dimerization
Synaptic Transmission
Conformations
Spectrum Analysis
Spectroscopy
Membranes
Molecules
dimerization
electrons
membranes

Bibliographical note

This article is licensed under a Creative Commons
Attribution 4.0 International License, which permits use, sharing,
adaptation, distribution and reproduction in any medium or format, as long as you give
appropriate credit to the original author(s) and the source, provide a link to the Creative
Commons license, and indicate if changes were made. The images or other third party
material in this article are included in the article’s Creative Commons license, unless
indicated otherwise in a credit line to the material. If material is not included in the
article’s Creative Commons license and your intended use is not permitted by statutory
regulation or exceeds the permitted use, you will need to obtain permission directly from
the copyright holder. To view a copy of this license, visit http://creativecommons.org/
licenses/by/4.0/.
© The Author(s) 2018

Cite this

Dijkman, P. M., Castell, O. K., Goddard, A., Munoz-Garcia, J. C., de Graaf, C., Wallace, M. I., & Watts, A. (2018). Dynamic tuneable G protein-coupled receptor monomer-dimer populations. Nature Communications, 9, [1710]. https://doi.org/10.1038/s41467-018-03727-6
Dijkman, Patricia M. ; Castell, Oliver K. ; Goddard, Alan ; Munoz-Garcia, Juan C. ; de Graaf, Chris ; Wallace, Mark I. ; Watts, Anthony. / Dynamic tuneable G protein-coupled receptor monomer-dimer populations. In: Nature Communications. 2018 ; Vol. 9.
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Dijkman, PM, Castell, OK, Goddard, A, Munoz-Garcia, JC, de Graaf, C, Wallace, MI & Watts, A 2018, 'Dynamic tuneable G protein-coupled receptor monomer-dimer populations' Nature Communications, vol. 9, 1710. https://doi.org/10.1038/s41467-018-03727-6

Dynamic tuneable G protein-coupled receptor monomer-dimer populations. / Dijkman, Patricia M.; Castell, Oliver K.; Goddard, Alan; Munoz-Garcia, Juan C.; de Graaf, Chris; Wallace, Mark I.; Watts, Anthony.

In: Nature Communications, Vol. 9, 1710, 27.04.2018.

Research output: Contribution to journalArticle

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Dijkman PM, Castell OK, Goddard A, Munoz-Garcia JC, de Graaf C, Wallace MI et al. Dynamic tuneable G protein-coupled receptor monomer-dimer populations. Nature Communications. 2018 Apr 27;9. 1710. https://doi.org/10.1038/s41467-018-03727-6