Structural analysis of the interaction between selenoprotein P and its receptors

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09822
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: National Institute for Physiological Sciences (2018-2019); Kanazawa University (2017)
• Principal Investigator: Kikuchi Akihiro 生理学研究所, 生体機能調節研究領域, 特任助教 (90321752)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: ２型糖尿病 / ヘパトカイン / セレノプロテイン / LDL受容体ファミリー / タンパク質間相互作用

Outline of Final Research Achievements

Selenoprotein P (SeP) is a diabetes-associated hepatokine. Analysis of the interaction between SeP and its receptors makes it possible to screen new compounds as potential anti-diabetic drugs. In this study, we have analyzed the interaction between SeP and its receptors such as ApoER2 by surface plasmon resonance (SPR) binding analysis.
SPR revealed the unique binding mode; 1) SeP binding to ApoER2 was quit strong, 2) the SeP binding site would not be the ligand binding domains but the other domains such as the beta-propeller domain in ApoER2. The strong binding of SeP to the receptor would have an advantage in uptake of selenium to cells. To investigate more details of the interaction, we are now trying to crystallize SeP/receptor complex. Also, the interaction between SeP and LRP1 that is the receptor in the skeletal muscle will be analyse by SPR.

Free Research Field

代謝・内分泌学

Academic Significance and Societal Importance of the Research Achievements

近年の増え続ける２型糖尿病に対し、従来の概念には依存しない新しい治療法の開発が求められている。肝臓から分泌されるセレノプロテインP（SeP）は２型糖尿病の病態を悪化させる要因の１つであり、SePの作用を阻害する化合物は新しい治療薬に結びつくと考えられる。
本研究ではSePと受容体との詳細な相互作用様式を検討した。その結果、SePは既知の様式とは全く異なる相互作用様式で受容体に結合することが明らかとなった。得られた知見はSePが受容体に結合できなくなるような化合物の探索に極めて有用な情報となる。