| 研究課題/領域番号 |
18K14665
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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) |
2018-04-01 – 2021-03-31
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| キーワード | ubiquitin / polyubiquitin / binding domains / protein dynamics / protein binding / nanosecond dynamics / millisecond dynamics / solution NMR |
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| 研究実績の概要 |
In this study we set out to characterize dynamic aspects of the ubiquitin code. The ubiquitin code (the relationship between ubiquitin-chain encoded intracellular signals and deciphering of these signals by other proteins containing ubiquitin-binding domains) is well established in the form of static snapshots most often derived from crystal structures. Here we provided additional "dynamic" aspects, i.e. we attempted to add a time-dimension to this static view.
Fo K48-linked chains we characterized all known structures of bound and free chains and find a large variety in structures which interconvert on the nanosecond timescale as shown in solution NMR experiments. These data are in agreement with a previous studies., but reveal additional asymmetric dynamics which were unexpected based on prior knowledge. A detailed account of this research is currently under review.
Other chains are still under investigation. In particular the dynamic binding mode of linear ubiquitin chains to their intracellular receptors is on-going. All experiments are finished, but the kinetic analysis requires slightly more time. It appears that the binding mode is more complex than previously anticipated. This is highly intriguing and will be reported in the near future.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
3: やや遅れている
理由
NMRやITC滴定実験において当初期待していた以上の結果が得られ、追加で論文化に必要なNMR緩和実験の必要性が出たためである。
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| 今後の研究の推進方策 |
We obtained several promising results on the dynamic recognition of ubiquitin chains by their binding partners. Several additional experiments, especially confirmation and control-type experiments are necessary, then the results of this current study can be published.
In the future we would like to expand this research to other ubiquitin chain types, in particular linear chains. In immune signaling pathways linear polyubiquitin chains play a special role and their dynamics and interactions with binding partners in solution have to be further explored to understand proper regulation (switching on- and off) of signaling pathways.
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| 次年度使用額が生じた理由 |
As pointed out in the research status report, several experiments are yet to be conducted. Moreover, publication of the results depends on these experiments; therefore publication fees have to be accounted for in the next fiscal year.
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