Structural Study of Human Dopamine D2 Receptor

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K18376
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Kyoto University
• Principal Investigator: Im Dohyun 京都大学, 医学研究科, 特定研究員 (50721883)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: Gタンパク質共役受容体 / GPCR / X線結晶構造解析 / 膜タンパク質

Outline of Final Research Achievements

The neurotransmitter dopamine controls numerous physiological functions in the brain and periphery via dopamine receptors in the G-protein-coupled receptor superfamily. Five dopamine receptors (DRD1-DRD5) are found in humans and DRD2 plays important pharmacological roles in numerous human disorders related to dopaminergic dysfunction, such as schizophrenia and Parkinson’s disease. In this study, we generate the functional antibody, which specifically recognizes DRD2, and we determined the ligand-free DRD2 structure using this antibody. This structure is believed to clarify the drug binding mechanism by comparison with already known antipsychotics binding structures. We also believe that it can help understand the mechanism of dopaminergic dysfunction.

Free Research Field

構造生物学

Academic Significance and Societal Importance of the Research Achievements

脳神経疾患の治療薬の標的として最も重要なターゲットタンパク質の一つであるドパミン受容体の立体構造解明と向精神薬との結合様式の解明は、今後新たな薬剤の開発への展開ができることで社会に貢献すると期待される。