| Budget Amount *help |
¥26,130,000 (Direct Cost: ¥20,100,000、Indirect Cost: ¥6,030,000)
Fiscal Year 2020: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2019: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2018: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2017: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
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| Outline of Final Research Achievements |
G-protein-coupled receptors (GPCRs) are seven-transmembrane proteins mediating cellular signals in response to extracellular stimuli. Although three-dimensional structures showcase snapshots that can be sampled in the process, the mechanism by which agonist-activated GPCRs interact with various effectors remains elusive. Here, we used nuclear magnetic resonance to visualize the structures of beta2-adrenergic receptor and adenosine A2A receptor. Analyses of efficacy-dependent chemical shifts of beta2-adrenergic receptor identified an equilibrium among three conformations, including one responsible for the varied signal level in each ligand-bound state. The docosahexanoic acid chains in lipid membranes redistribute the multiple conformations of adenosine A2A receptor toward those preferable for G protein binding. These results provide a structural basis for the dynamic activation of GPCRs and shed light on GPCR-mediated signal transduction.
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