NDLI: Heterodimerization with Its splice variant blocks the ghrelin receptor 1a in a non-signaling conformation: a study with a purified heterodimer assembled into lipid discs.

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Heterodimerization with Its splice variant blocks the ghrelin receptor 1a in a non-signaling conformation: a study with a purified heterodimer assembled into lipid discs.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Fehrentz, Jean-alain Martinez, Jean Gaibelet, Gérald Verdié, Pascal Orcel, Hélène Damian, Marjorie Mouillac, Bernard Marie, Jacky Mary, Sophie Banères, Jean-louis
Description	Author Affiliation: Mary S ( Institut des Biomolécules Max Mousseron (IBMM), CNRS UMR 5247, Université Montpellier 1, Faculté de Pharmacie, 15 avenue Charles Flahault, BP 14491, 34093 Montpellier Cedex 5, France.)
Abstract	Heterodimerization of G protein-coupled receptors has an impact on their signaling properties, but the molecular mechanisms underlying heteromer-directed selectivity remain elusive. Using purified monomers and dimers reconstituted into lipid discs, we explored how dimerization impacts the functional and structural behavior of the ghrelin receptor. In particular, we investigated how a naturally occurring truncated splice variant of the ghrelin receptor exerts a dominant negative effect on ghrelin signaling upon dimerization with the full-length receptor. We provide direct evidence that this dominant negative effect is due to the ability of the non-signaling truncated receptor to restrict the conformational landscape of the full-length protein. Indeed, associating both proteins within the same disc blocks all agonist- and signaling protein-induced changes in ghrelin receptor conformation, thus preventing it from activating its cognate G protein and triggering arrestin 2 recruitment. This is an unambiguous demonstration that allosteric conformational events within dimeric assemblies can be directly responsible for modulation of signaling mediated by G protein-coupled receptors.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	34
Volume Number	288
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2013-08-23
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Lipid Bilayers Protein Multimerization Receptors, Ghrelin Chemistry Alternative Splicing Genetics Animals Arrestin Metabolism Protein Conformation Protein Structure, Quaternary Sf9 Cells Spodoptera Research Support, Non-U.S. Gov't Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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