• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Structural analysis of the interaction between selenoprotein P and its receptors

Research Project

Project/Area Number 17K09822
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Metabolomics
Research InstitutionNational 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
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords2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 / 2型糖尿病 / タンパク質結晶構造解析 / タンパク質間相互作用解析 / 糖尿病 / 結晶構造解析 / 相互作用解析
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.

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。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (12 results)

All 2019 2018 2017

All Journal Article (5 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (5 results) Book (2 results)

  • [Journal Article] Circulating Concentrations of Insulin Resistance-Associated Hepatokines, Selenoprotein P and Leukocyte Cell-Derived Chemotaxin 2, during an Oral Glucose Tolerance Test in Humans2019

    • Author(s)
      Mohri K, Misu H, Takayama H, Ishii KA, Kikuchi A, Lan F, Enyama Y, Takeshita Y, Saito Y, Kaneko S,Takamura T.
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 42 Issue: 3 Pages: 373-378

    • DOI

      10.1248/bpb.b18-00549

    • NAID

      130007607371

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2019-03-01
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The clinical course and potential underlying mechanisms of everolimus-induced hyperglycemia2019

    • Author(s)
      Tanimura Jun、Nakagawa Hiromi、Tanaka Takeo、Kikuchi Akihiro、Osada Sachie、Tanaka Yoshiaki、Tokuyama Kumpei、Takamura Toshinari
    • Journal Title

      Endocrine Journal

      Volume: 66 Issue: 7 Pages: 615-620

    • DOI

      10.1507/endocrj.EJ18-0542

    • NAID

      130007684324

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clonal hematopoiesis by SLIT1-mutated hematopoietic stem cells due to a breakdown of the autocrine loop involving Slit1 in acquired aplastic anemia2019

    • Author(s)
      Hosokawa K, Mizumaki H, Elbadry M, Saito C, Espinoza JL, An DTT, Katagiri T, Harashima A, Kikuchi A, Kanai A, Matsui H, Inaba T, Taniwaki M, Yamamoto Y, Nakao S
    • Journal Title

      Leukemia

      Volume: 33 Issue: 11 Pages: 2732-2766

    • DOI

      10.1038/s41375-019-0510-0

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] p62-mediated autophagy affects nutrition-dependent insulin receptor substrate 1 dynamics in 3T3-L1 preadipocytes2019

    • Author(s)
      Igawa Hirobumi、Kikuchi Akihiro、Misu Hirofumi、Ishii Kiyo-aki、Kaneko Shuichi、Takamura Toshinari
    • Journal Title

      Journal of Diabetes Investigation

      Volume: 10 Issue: 1 Pages: 32-42

    • DOI

      10.1111/jdi.12866

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibin betaE (INHBE) is a possible insulin resistance-associated hepatokine identified by comprehensive gene expression analysis in human liver biopsy samples2018

    • Author(s)
      M. Sugiyama, A. Kikuchi, H. Misu, H. Igawa, M. Ashihara, Y. Kushima, K. Honda, Y. Suzuki, Y. Kawabe, S. Kaneko and T. Takamura
    • Journal Title

      PLoS One

      Volume: 13 Issue: 3 Pages: e0194798-e0194798

    • DOI

      10.1371/journal.pone.0194798

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 肥満関連ヘパトカインLECT2のマウスにおける血中半減期および体内動態2019

    • Author(s)
      菊地 晶裕、高山 浩昭、柴 和弘、御簾 博文、篁 俊成
    • Organizer
      第62回日本糖尿病学会年次学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 肝脂肪化を感知するヘパトカインLECT2のマウスにおける体内動態2019

    • Author(s)
      菊地 晶裕、 高山 浩昭、 柴 和弘、 御簾 博文、 箕越 靖彦、 篁 俊成
    • Organizer
      第40回日本肥満学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] インスリン受容体基質(IRS-1)の栄養依存的タンパク質発現変動における選択的オートファジー受容体p62介在性オートファジーの役割2018

    • Author(s)
      井川 寛章、 菊地 晶裕、 御簾 博文、石井 清明、 金子 周一、 篁 俊成
    • Organizer
      第61回日本糖尿病学会年次学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 新規な肥満関連ヘパトカインinhibin βEの同定と機能解析2018

    • Author(s)
      菊地 晶裕、 御簾 博文、 井川 寛章、 篁 俊成
    • Organizer
      第39回日本肥満学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 病態形成ヘパトカインLECT2のマウスにおける体内動態2018

    • Author(s)
      菊地 晶裕、 高山 浩昭、 津金 寛彦、 Swe Mar Oo、 御簾 博文、 柴 和弘、 篁 俊成
    • Organizer
      学際科学実験センターシンポジウム
    • Related Report
      2017 Research-status Report
  • [Book] セレノプロテインPの新たな機能と受容体 (「内分泌・糖尿病・代謝内科」 Vol.44, No 5の話題を担当)2017

    • Author(s)
      菊地 晶裕、 篁 俊成
    • Total Pages
      8
    • Publisher
      科学評論社
    • Related Report
      2017 Research-status Report
  • [Book] 肝臓の糖・エネルギー代謝 (「Diabetes Frontier」 Vol.28, No.6の特集「糖尿病と肝臓」を分担)2017

    • Author(s)
      菊地 晶裕、 篁 俊成
    • Total Pages
      7
    • Publisher
      メディカルレビュー社
    • ISBN
      9784779220203
    • Related Report
      2017 Research-status Report

URL: 

Published: 2017-04-28   Modified: 2021-02-19  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi