Structural elucidation of the mechanism underlying biased signaling of GPCRs
Project/Area Number |
25460033
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Research Category |
Grant-in-Aid for Scientific Research (C)
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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
|
Project Status |
Completed (Fiscal Year 2015)
|
Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
Keywords | GPCR / NMR / 膜タンパク質 / 構造生物学 / 膜蛋白質 / 蛋白質 / 薬学 / シグナル伝達 |
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.
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Report
(4 results)
Research Products
(14 results)
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[Journal Article] Conductance of P2X4 receptor is determined by conformational equilibrium in the transmembrane region2016
Author(s)
Minato Y, Suzuki S , Hara T, Kofuku Y, Kasuya G, Fujiwara Y, Igarashi S, Suzuki E, Nureki O, Hattori M, Ueda T, Shimada I
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Journal Title
Proc. Natl. Acad. Sci.
Volume: 発行中
Issue: 17
Pages: 4741-4746
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Identification of a Conformational Equilibrium That Determines the Efficacy and Functional Selectivity of the μ-Opioid Receptor.2015
Author(s)
Junya Okude, Takumi Ueda, Yutaka Kofuku, Motohiko Sato, Naoyuki Nobuyama, Keita Kondo, Yutaro Shiraishi, Takuya Mizumura, Kento Onishi, Mei Natsume, Masahiro Maeda, Hideki Tsujishita, Takefumi Kuranaga, Masayuki Inoue, Ichio Shimada
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Journal Title
Angewandte Chemie International Edition
Volume: 21
Issue: 52
Pages: 15771-15776
DOI
Related Report
Peer Reviewed / Open Access
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