2019 Fiscal Year Research-status Report
Dynamic Character of the Ubiquitin System
| Project/Area Number |
18K14665
|
|---|
| Research Institution | Kyoto University |
|---|
Principal Investigator |
Walinda Erik 京都大学, 医学研究科, 助教 (80782391)
|
|---|
| Project Period (FY) |
2018-04-01 – 2021-03-31
|
| Keywords | ubiquitin / polyubiquitin / binding domains / protein dynamics / protein binding / nanosecond dynamics / millisecond dynamics / solution NMR |
|---|
| Outline of Annual Research Achievements |
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.
|
| Current Status of Research Progress |
Current Status of Research Progress
3: Progress in research has been slightly delayed.
Reason
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。
|
| Strategy for Future Research Activity |
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.
|
| Causes of Carryover |
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.
|
Research Products
(2 results)
