Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 53, Issue 49, Pages 13376-13379Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201406603
Keywords
G-protein-coupled receptors; isotopic labeling; lipid bilayers; membrane proteins; NMR spectroscopy
Categories
Funding
- Japan New Energy and Industrial Technology Development Organization (NEDO)
- Ministry of Economy, Trade and Industry (METI)
- Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT)
- Grants-in-Aid for Scientific Research [26893041, 25460033, 21121001, 26120506] Funding Source: KAKEN
Ask authors/readers for more resources
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 beta 2-adrenergic receptor (beta(2)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 beta(2)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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available