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2016 Fiscal Year Final Research Report

Structure and functional study of the agonist-bound dopamine D1 receptor for the development of antiparkinson

Research Project

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Project/Area Number 15K18486
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Structural biochemistry
Research InstitutionKyoto University

Principal Investigator

Fujiwara Takaai  京都大学, 医学研究科, 特定研究員 (70712751)

Research Collaborator Shimamura TATSURO  
Morimoto SHIHO  
Project Period (FY) 2015-04-01 – 2017-03-31
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
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.

Free Research Field

構造生物化学

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Published: 2018-03-22  

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