2022 Fiscal Year Final Research Report
Development of a system that selectively unfolds and degrades a targeted protein or its aggregate
Project/Area Number |
20K06566
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 43030:Functional biochemistry-related
|
Research Institution | Konan University |
Principal Investigator |
|
Project Period (FY) |
2020-04-01 – 2023-03-31
|
Keywords | タンパク質 / 選択的分解 / 凝集体 / 脱凝集 / アミロイド |
Outline of Final Research Achievements |
Techniques to selectively degrade any targeted protein are useful for studying the role of specific proteins. One existing technique is to target proteins to the ubiquitin-proteasome system, but its application is limited. In this study, we aimed to construct a new selective proteolytic system by integrating nanobody that bind target proteins, ClpB chaperone that unfold the bound proteins, and Lon protease that degrade them. In this study, we were able to functionally fuse the ClpB and the protease domain of Lon. On the other hand, the nanobody fusion destabilised the protein. Other methods to bind target proteins need to be explored.
|
Free Research Field |
タンパク質科学
|
Academic Significance and Societal Importance of the Research Achievements |
本研究で作製を目指した、任意のタンパク質を選択的にアンフォールド・脱凝集・分解するT-ProUDシステムは、特定のタンパク質や、そのアミロイドの役割を調べるための強力なツールとなる。特に、単一のタンパク質で構成されている点、ユビキチン・プロテアソーム系のない原核生物や細胞外でも利用できる点、分解を伴わない凝集状態の制御を行える点は、既存の選択的タンパク質分解系にはない特徴である。本研究において、ClpBとLonのプロテアーゼドメインを機能を持った形で融合させることができたことで、T-ProUDシステムの完成に大きく近づいたと言える。
|