Functional dynamics of deuterated ß2 -adrenergic receptor in lipid bilayers revealed by NMR spectroscopy.
Angew Chem Int Ed Engl
; 53(49): 13376-9, 2014 Dec 01.
Article
em En
| MEDLINE
| ID: mdl-25284766
ABSTRACT
G-protein-coupled receptors (GPCRs) exist in conformational equilibrium between active and inactive states, and the former population determines the efficacy of signaling. However, the conformational equilibrium of GPCRs in lipid bilayers is unknown owing to the low sensitivities of their NMR signals. To increase the signal intensities, a deuteration method was developed for GPCRs expressed in an insect cell/baculovirus expression system. The NMR sensitivities of the methionine methyl resonances from the ß2 -adrenergic receptor (ß2 AR) in lipid bilayers of reconstituted high-density lipoprotein (rHDL) increased by approximately 5-fold upon deuteration. NMR analyses revealed that the exchange rates for the conformational equilibrium of ß2 AR in rHDLs were remarkably different from those measured in detergents. The timescales of GPCR signaling, calculated from the exchange rates, are faster than those of receptor tyrosine kinases and thus enable rapid neurotransmission and sensory perception.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Receptores Adrenérgicos beta 2
/
Ressonância Magnética Nuclear Biomolecular
/
Bicamadas Lipídicas
/
Lipoproteínas HDL
Limite:
Animals
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Ano de publicação:
2014
Tipo de documento:
Article