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Functional Modulation of a G Protein-Coupled Receptor Conformational Landscape in a Lipid Bilayer
- Source :
- Journal of the American Chemical Society, Journal of the American Chemical Society, American Chemical Society, 2016, 138 (35), pp.11170-11175. ⟨10.1021/jacs.6b04432⟩
- Publication Year :
- 2016
-
Abstract
- International audience; Mapping the conformational landscape of G protein-coupled receptors (GPCRs), and in particular how this landscape is modulated by the membrane environment, is required to gain a clear picture of how signaling proceeds. To this end, we have developed an original strategy based on solution-state nuclear magnetic resonance combined with an efficient isotope labeling scheme. This strategy was applied to a typical GPCR, the leukotriene B4 receptor BLT2, reconstituted in a lipid bilayer. Because of this, we are able to provide direct evidence that BLT2 explores a complex landscape that includes four different conformational states for the unliganded receptor. The relative distribution of the different states is modulated by ligands and the sterol content of the membrane, in parallel with the changes in the ability of the receptor to activate its cognate G protein. This demonstrates a conformational coupling between the agonist and the membrane environment that is likely to be fundamental for GPCR signaling.
- Subjects :
- 0301 basic medicine
Agonist
Models, Molecular
medicine.drug_class
G protein
Stereochemistry
Protein Conformation
[SDV]Life Sciences [q-bio]
Lipid Bilayers
Receptors, Leukotriene B4
010402 general chemistry
Ligands
01 natural sciences
Biochemistry
Catalysis
03 medical and health sciences
Colloid and Surface Chemistry
Allosteric Regulation
medicine
[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
Receptor
Lipid bilayer
G protein-coupled receptor
Chemistry
Leukotriene B4 receptor
General Chemistry
0104 chemical sciences
Coupling (electronics)
030104 developmental biology
Membrane
Biophysics
Signal Transduction
Subjects
Details
- ISSN :
- 15205126 and 00027863
- Volume :
- 138
- Issue :
- 35
- Database :
- OpenAIRE
- Journal :
- Journal of the American Chemical Society
- Accession number :
- edsair.doi.dedup.....135cb66c79fd83e7a5af074259c1b765