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Structural biology of inflammatory response

Research Project

Project/Area Number 16H04752
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Structural biochemistry
Research InstitutionKyoto University

Principal Investigator

Tochio Hidehito  京都大学, 理学研究科, 教授 (70336593)

Research Collaborator Ohnishi Hidenori  
Konno Hiroki  
Mayanagi Kouta  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2018: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2017: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2016: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
KeywordsIL-18 / MyD88 / タンパク質 / 炎症 / NMR / AFM / 結晶構造解析 / 高速AFM / TIR / 構造生物学 / IL-37 / X線結晶構造解析 / 蛋白質
Outline of Final Research Achievements

The interdomain interaction within the molecule of MyD88 was revealed by AFM observation and NMR spectroscopy. The interaction sites were also identified by mutagenesis. In addition, it was found by using NMR that the propeptide portion of the precursor of IL-18 extensively interacted with the main body of IL-18. CD spectra and NMR measurements revealed that the thermodynamic stability of the precursor was higher than that of mature IL-18. A peptide containing the propeptide sequence was found to bind to IL-18, reproducing the interaction seen in the precusor of IL-18. In addition, the crystal structure of IL-37 was determined.

Academic Significance and Societal Importance of the Research Achievements

MyD88はIL-1ファミリーやToll様受容体のシグナル伝達にとって重要なアダプタータンパク質である。今回、MyD88がOpenとCloseの2つの状態をとることを初めて明らかにした。このスイッチングが、MyD88下流のシグナル伝達制御に利用されている可能性があり、MyD88が関わる多様なシグナル伝達の研究にとって極めて意義深いものだと考えられる。
IL-18や他のIL-1ファミリーの前駆体に関する構造情報はほとんどなかったため、本研究で得られた情報は貴重である。特に、IL-1ファミリーのpropeptideと本体の相互作用を明らかにした例は初めてであり、今後の研究を促すものである。

Report

(3 results)
  • 2018 Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (6 results)

All 2017 2016

All Presentation (5 results) (of which Int'l Joint Research: 3 results,  Invited: 3 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Presentation] 免疫シグナルハブタンパク質MyD88の分子内相互作用解析2017

    • Author(s)
      宇野雅俊
    • Organizer
      2017年度生命科学系学会合同年次大会(Conbio2017)
    • Related Report
      2017 Annual Research Report
  • [Presentation] Analysis of proteins in living mammalian cells with NMR spectroscopy.2017

    • Author(s)
      杤尾豪人
    • Organizer
      The 2nd International Symposium on Biofunctional Chemistry(ISBC2017)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 抗炎症性サイトカインIL-37の構造解析2017

    • Author(s)
      今村香代
    • Organizer
      第6回岐阜構造生物学・医学・論理的創薬研究会シンポジウム
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Functional study of an unique member of the IL-1 family cytokines2017

    • Author(s)
      今村香代
    • Organizer
      第42回内藤コンファレンス"In the Vanguard of Structural Biology: Revolutionizing Life Sciences"
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Structural study of proinflammatory cytokine Interleukin-182016

    • Author(s)
      杤尾豪人
    • Organizer
      第42回内藤コンファレンス"In the Vanguard of Structural Biology: Revolutionizing Life Sciences"
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Patent(Industrial Property Rights)] インターロイキン-18活性阻害剤2016

    • Inventor(s)
      杤尾豪人、堤尚孝、横田歩、大西秀典、木村豪、加藤善一郎
    • Industrial Property Rights Holder
      国立大学法人京都大学、国立大学法人岐阜大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2016
    • Related Report
      2016 Annual Research Report
    • Overseas

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Published: 2016-04-21   Modified: 2020-03-30  

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