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2018 Fiscal Year Final Research Report

Structural biology of inflammatory response

Research Project

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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
KeywordsIL-18 / MyD88
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.

Free Research Field

構造生物学

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。

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Published: 2020-03-30  

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