2023 Fiscal Year Research-status Report
Regulation of NF-kB signaling through competitive interactions against linear polyubiquitin
| Project/Area Number |
22K06161
|
|---|
| Research Institution | Kyoto University |
|---|
Principal Investigator |
Walinda Erik 京都大学, 医学研究科, 助教 (80782391)
|
|---|
| Project Period (FY) |
2022-04-01 – 2025-03-31
|
| Keywords | ubiquitin / linear ubiquitin / ubiquitin binding / M1-linked chains |
|---|
| Outline of Annual Research Achievements |
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.
|
| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
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.
|
| Strategy for Future Research Activity |
We will continue to dissect the kinetics of ubiquitin recognition by HOIL-1L and similar ubiquitin-binding proteins by using biophysical methods.
|
| Causes of Carryover |
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.
|
