| Project/Area Number |
15H06325
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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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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| Project Period (FY) |
2015-08-28 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 翻訳 / 蛋白質 / リン酸化 / 分子動力学シミュレーション / 生物物理 / RNA / 翻訳制御 / RNA結合蛋白質 |
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| Outline of Final Research Achievements |
Under stress conditions, since eukaryotic cell is necessary to minimize its energy consumption, novel protein synthesis, called translation, is limited. This process is engaged in mTORC1-mediated phosphorylation. Activated mTORC1 kinase phosphorylates its substrates such as LARP1 or 4E-BP1 and regulates translation efficiency of mRNAs through alteration of protein-protein interactions.
In this study, we investigated how mTORC1-mediated phosphorylation changes the 4E-BP1/eIF4E interaction. We used MD simulations to calculate structural changes of unphospho- or phosphorylated-4E-BP1 complexed with eIF4E. The results showed that 4E-BP1 phosphorylation at S65 and T70 sites caused structural change in the C-terminal tail of 4E-BP1, and inhibited the interaction with the N-terminal tail, a-2 helix and b-2 strand of eIF4E. These results correspond to experimental data, and thus MD simulations provides atomic insights into phospho-4E-BP1/eIF4E complex structures.
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