Functional Modulation of a G Protein-Coupled Receptor Conformational Landscape in a Lipid Bilayer.
J Am Chem Soc
; 138(35): 11170-5, 2016 09 07.
Article
en En
| MEDLINE
| ID: mdl-27489943
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Receptores de Leucotrieno B4
/
Membrana Dobles de Lípidos
Idioma:
En
Revista:
J Am Chem Soc
Año:
2016
Tipo del documento:
Article
País de afiliación:
Francia