| Project/Area Number |
17K15434
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Physical pharmacy
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| Research Institution | Kyoto University |
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Principal Investigator |
Kamba Keisuke 京都大学, エネルギー理工学研究所, 研究員 (00795049)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 生体分子 / NMR / 相互作用 / APOBEC3G / HIV / Vif / 阻害 / タンパク質複合体 / 選択的標識 |
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| Outline of Final Research Achievements |
Human APOBEC3G (A3G) protein deaminates a cytosine within minus DNA of HIV, and thereby restricts the infectivity of viral-infectivity-factor (Vif)-deficient HIV strains. A3G comprises a catalytically inactive N-terminal domain (NTD) and an active C-terminal domain (CTD).
HIV Virion infectivity factor (Vif) protein completely suppresses A3G. Vif is an intrinsically disordered protein, forming a five-membered complex (Vif complex) by hijacking the components of four human proteins. Vif reportedly binds to NTD of A3G, ubiquitinates CTD of A3G, then degrades A3G through ubiquitin-proteasome proteolysis
In this study one protein was selectively isotope labeled for NMR study. It was also found that Vif complex directly inhibit deamination activity of A3G. To understand the mechanism, the interaction between A3G, Vif complex, and ssDNA were investigated. The interaction between A3G CTD and Vif complex, including human proteins would be important for A3G inhibition.
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| Academic Significance and Societal Importance of the Research Achievements |
複合体タンパク質の単独の分子を標識する手法を提供することで、NMRを用いて高分子量のタンパク質を標識することが可能になり、ドラッグスクリーニング等に応用できることが期待される。宿主分子を巧みに利用するウイルス分子の作用機序を明らかにすることで、創薬研究のみならず、生命の進化の本質にかかわる知見が得られることが期待される。
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