| Project/Area Number |
15K18843
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Physical pharmacy
|
|---|
| Research Institution | The University of Tokyo |
|---|
Principal Investigator |
KOFUKU Yutaka 東京大学, 大学院薬学系研究科(薬学部), 特任助教 (80737940)
|
|---|
| Project Period (FY) |
2015-04-01 – 2017-03-31
|
| Project Status |
Completed (Fiscal Year 2016)
|
| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
|---|
| Keywords | 構造生物学 / NMR / 膜タンパク質 / シグナル伝達 / GPCR |
|---|
| Outline of Final Research Achievements |
G-protein-coupled receptor (GPCR) ligands impart differing degrees of signaling in the G-protein and arrestin pathways, in phenomena called "biased signaling". However, the mechanism underlying the biased signaling of GPCRs is still unclear, although crystal structures of GPCRs bound to the G protein or arrestin are available. In this study, we observed the NMR signals from methionine residues of pharmacologically important GPCRs in the balanced- and biased-ligand-bound states. We found that the intracellular cavity of GPCRs exist in an equilibrium between closed and multiple open conformations, and that the population of each open conformation determines the G-protein- and arrestin-mediated signaling levels in each ligand-bound state.
|
