Structural analysis of amine receptors for the development of new antipsychotic drugs.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02414
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 43020:Structural biochemistry-related
• Research Institution: Kyoto University
• Principal Investigator: Shimamura Tatsuro 京都大学, 医学研究科, 特定准教授 (90391979)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 受容体

Outline of Final Research Achievements

G protein-coupled receptors exist in equilibrium between active and inactive forms and exhibit a certain basic activity even without ligand binding. Inverse agonists exist in a wide range of potencies, from strong to weak, but the relationship between such differences in potency and structure is unknown. In this study, we determined the complex structure of the serotonin receptor with a weak inverse agonist. The results revealed that in the bound state of this inverse agonist, the structure is closer to the active conformation than to the inactive conformation.

Free Research Field

構造生物学

Academic Significance and Societal Importance of the Research Achievements

少なくとも一部のGタンパク質共役型受容体では、完全逆作動薬や部分逆作動薬のように、結合する逆作動薬の効力の強弱により複数の不活性型構造が存在することが示唆されている。本研究の成果は、逆作動薬の強弱がGタンパク質共役型受容体の構造の違いに由来する可能性を示唆し、Gタンパク質共役型受容体の機能の理解などに貢献すると考えられる。