2018 Fiscal Year Final Research Report
The structural analysis of beta2-microglobulin amyloid fibril
| Project/Area Number |
17K15074
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Structural biochemistry
|
|---|
| Research Institution | Osaka University |
|---|
Principal Investigator |
So Masatomo 大阪大学, 蛋白質研究所, 助教 (40746335)
|
|---|
| Research Collaborator |
Matsuki Yoh
Tamaki Hajime
Iwasaki Kenji
Kawamoto Akihiro
|
|---|
| Project Period (FY) |
2017-04-01 – 2019-03-31
|
| Keywords | アミロイド線維 / β2‐ミクログロブリン / 固体NMR / クライオ電子顕微鏡 |
|---|
| Outline of Final Research Achievements |
β2 microglobulin amyloid fibrils, which is associated to dialysis related amyloidosis, has high heterogeneity compared to other fibrils whose structure has been reported, disturbing structural analysis. In this study, I prepared the homogeneous fibrils and obtained NMR spectra with sparse signals enabling the signal assignment of more than 80 % residues of the fibril core. I further combined cryo-EM analysis, which have been developing and applied to amyloid fibrils analysis, with NMR analysis and constructed model structure. In order to increase the importance of the investigation, I will prepare fibrils samples using fibrils obtained from patients and analyze the structure of fibrils under physiological conditions.
|
| Free Research Field |
構造生物学
|
| Academic Significance and Societal Importance of the Research Achievements |
アミロイド線維構造を明らかにすることは病気の発症機序を明らかにするうえで欠かせない情報である。本研究で用いるβ2ミクログロブリンはすでに報告されているアミロイドペプチドに比べ構造解析が困難であった。それを試料作製技術やクライオ電子顕微鏡など最新技術を駆使して克服し、構造モデルを構築することで、アミロイド形成機構全体を明らかにする第一歩となるとともに、他のアミロイド線維構造解析に役立つ技術を提供でき、アミロイド線維形成全体の理解に役立つ。
|
