Functional Dynamics of Deuterated β2‐Adrenergic Receptor in Lipid Bilayers Revealed by NMR Spectroscopy1. Issue 49 (3rd October 2014)

• Record Type: Journal Article
• Authors: Kofuku, Yutaka; Ueda, Takumi; Okude, Junya; Shiraishi, Yutaro; Kondo, Keita; Mizumura, Takuya; Suzuki, Shiho; Shimada, Ichio
• Is Part Of: Angewandte Chemie international edition. Volume 53:Issue 49(2014)
• Page Start: 13376
• Page End: 13379
• Publication Date: 2014-10-03
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201406603
• Languages: English
• ISSNs: 1433-7851

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>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 β₂‐adrenergic receptor (β₂AR) 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 β₂AR 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.</p> </abstract>