Receptor specificity and self-association of arrestin

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K07319
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biophysics
• Research Institution: Kyoto University
• Principal Investigator: Imamoto Yasushi 京都大学, 理学研究科, 准教授 (80263200)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: アレスチン / G蛋白質共役型受容体 / GPCR / 自己会合 / X線溶液散乱法 / p44

Outline of Final Research Achievements

The interaction between rhodopsin, a typical G-protein coupled receptor, and arrestin was studied by small-angle X-ray scattering using nanodiscs. The comparison of self-association and interaction with phosphorylated rhodopsin between rod arrestin and its splice variant p44 suggested that p44 forms tetramer similar to that of arrestin. In addition, it was experimentally demonstrated that p44 and phosphorylated rhodopsin form unstable complex (pre-coupled state) in the dark, which is converted to fully coupled state by light.

Free Research Field

生物物理学、光生物学

Academic Significance and Societal Importance of the Research Achievements

GPCRは市販の医薬品の約半数が作用していると考えられている生理学的・薬理学的に重要な蛋白質群である。GPCRはリガンドの作用によってG蛋白質で仲介される細胞内シグナル伝達系を活性化し、リン酸化とアレスチン結合によってG蛋白質活性化能を失う。本研究で得られたアレスチンのタイプの違いによる結合様式の違いは、GPCRの活性を適切に制御して細胞が正常に機能するメカニズムの理解に寄与すると考えられる。