| 研究課題/領域番号 |
22K06161
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| 研究機関 | 京都大学 |
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研究代表者 |
Walinda Erik 京都大学, 医学研究科, 助教 (80782391)
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| 研究期間 (年度) |
2022-04-01 – 2025-03-31
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| キーワード | ubiquitin / linear ubiquitin / ubiquitin binding / M1-linked chains |
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| 研究実績の概要 |
Focusing on the linear ubiquitin chain assembly complex, we elucidate how it synthesizes "head-to-tail" poly-Ub chains crucial for immune signaling and cell death regulation. Specifically, we investigate the interaction between HOIL-1L and linear poly-Ub chains, revealing the molecular determinants driving their selective binding. Through NMR and biophysical methods, we unveil the dynamic process by which the NZF domain of HOIL-1L evolves into the specific linear di-Ub-bound state while excluding other potential Ub species. Our findings highlight the role of conserved electrostatic contacts and the impact of phosphorylation at threonine-207 on linear Ub affinity. This research deepens our understanding of the Ub code and offers insights valuable for immune diseases and cancer research.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
Overall, the research is progressing smoothly. However, further analysis and validation experiments are needed. While we are making large progress on understanding the kinetics of binary systems, consisiting of ubiquitin chains and their rececptors, it is tricky to dissect the competitve systems. However, we have experiments lined up that can surely elucidate this elusive mechanism.
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| 今後の研究の推進方策 |
We will continue to dissect the kinetics of ubiquitin recognition by HOIL-1L and similar ubiquitin-binding proteins by using biophysical methods.
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| 次年度使用額が生じた理由 |
Several items to be purchased for protein purification systems (centrifuge rotors etc.) became priced less expensively than originally calculated. Thus, this capital has been allocated to the subsequent fiscal year to be used in other experiments.
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