Allosteric modulation of ghrelin receptor signaling by lipids

Marjorie Damian, Maxime Louet, Antoniel Augusto Severo Gomes, Céline M’Kadmi, Séverine Denoyelle, Sonia Cantel, Sophie Mary, Paulo M. Bisch, Jean-Alain Fehrentz, Laurent J. Catoire, Nicolas Floquet and Jean-Louis Banères ()
Additional contact information
Marjorie Damian: Université de Montpellier, ENSCM
Maxime Louet: Université de Montpellier, ENSCM
Antoniel Augusto Severo Gomes: Université de Montpellier, ENSCM
Céline M’Kadmi: Université de Montpellier, ENSCM
Séverine Denoyelle: Université de Montpellier, ENSCM
Sonia Cantel: Université de Montpellier, ENSCM
Sophie Mary: Université de Montpellier, ENSCM
Paulo M. Bisch: Universidade Federal do Rio de Janeiro
Jean-Alain Fehrentz: Université de Montpellier, ENSCM
Laurent J. Catoire: Université de Paris, Institut de Biologie Physico-Chimique (FRC 550)
Nicolas Floquet: Université de Montpellier, ENSCM
Jean-Louis Banères: Université de Montpellier, ENSCM

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: Abstract The membrane is an integral component of the G protein-coupled receptor signaling machinery. Here we demonstrate that lipids regulate the signaling efficacy and selectivity of the ghrelin receptor GHSR through specific interactions and bulk effects. We find that PIP2 shifts the conformational equilibrium of GHSR away from its inactive state, favoring basal and agonist-induced G protein activation. This occurs because of a preferential binding of PIP2 to specific intracellular sites in the receptor active state. Another lipid, GM3, also binds GHSR and favors G protein activation, but mostly in a ghrelin-dependent manner. Finally, we find that not only selective interactions but also the thickness of the bilayer reshapes the conformational repertoire of GHSR, with direct consequences on G protein selectivity. Taken together, this data illuminates the multifaceted role of the membrane components as allosteric modulators of how ghrelin signal could be propagated.

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (4)

Downloads: (external link)
https://www.nature.com/articles/s41467-021-23756-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23756-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-23756-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().