Structural biology of inflammatory response
| Project/Area Number |
16H04752
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Structural biochemistry
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Research Collaborator |
Ohnishi Hidenori
Konno Hiroki
Mayanagi Kouta
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| 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)
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| Keywords | IL-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 |
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| 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.
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| 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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Report
(3 results)
Research Products
(6 results)
