Structure and functional study of the agonist-bound dopamine D1 receptor for the development of antiparkinson
| Project/Area Number |
15K18486
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Structural biochemistry
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Research Collaborator |
Shimamura TATSURO
Morimoto SHIHO
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 構造生物 / 膜タンパク質 / X線結晶構造解析 / Gタンパク質共役受容体 / アミン受容体 / シグナル伝達 / タンパク質構造安定化 / キメラタンパク質 / 部位特異的変異導入 |
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| Outline of Final Research Achievements |
The dopamine D1 receptor is one of the drug target for neurodegenerative disorders including Parkinson's disease. The structural information of the D1 receptor provides insights into the ligand recognition, which leads to the development of the novel drug for the treatment of Parkinson's disease. The aim of this study is to reveal the structure of the D1 receptor bound to an agonist as a potential antiparkinson drug. We designed expression constructs of the D1 receptor with fusion proteins into the disordered loops of the receptor. Then, we solubilized engineered receptor constructs and purified them. Further investigation for improvement of the yield of the purified receptors allows to accomplish crystallization and the following structure determination of the D1 receptor hearafter. On the other hands, we successfully crystallized the histamine H1 receptor, and determined the structures of the H1 receptor bound to the ligand, which reveled the interaction manner of the ligand.
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Report
(3 results)
Research Products
(2 results)
