2015 Fiscal Year Final Research Report
Structural elucidation of the mechanism underlying biased signaling of GPCRs
Project/Area Number |
25460033
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Physical pharmacy
|
Research Institution | The University of Tokyo |
Principal Investigator |
Ueda Takumi 東京大学, 薬学研究科(研究院), 助教 (20451859)
|
Co-Investigator(Kenkyū-buntansha) |
Ichio Shimada 東京大学, 大学院薬学系研究科, 教授 (70196476)
|
Project Period (FY) |
2013-04-01 – 2016-03-31
|
Keywords | GPCR / NMR / 膜タンパク質 |
Outline of Final Research Achievements |
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. We could also identified conformational equilibrium of GPCRs that determine their biased signaling.
|
Free Research Field |
構造生物学
|