Video-imaging of amyloid disaggregase, Hsp104, on amyloid fibrils

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K18524
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biophysics
• Research Institution: Kanazawa University
• Principal Investigator: Nakayama Takahiro 金沢大学, ナノ生命科学研究所, 准教授 (00532821)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: アミロイドタンパク / 原子間力顕微鏡

Outline of Final Research Achievements

Yeast Hsp104 has been known to be the disaggregase which disaggregates various insoluble amyloid fibrils with different fibril structures. The mechanism of this diverse substrate specificity, however, has been unclarified. In this study, we tried to observe structural dynamics of individual Hsp104 and amyloid fibrils on amyloid disaggregase reaction, using high-speed atomic force microscopy (HS-AFM). We observed structural dynamics of amyloidogenic protein X aggregation into fibrils while we have not been able to characterize the disaggregation events on HS-AFM movies.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

アミロイドタンパクX凝集過程の構造動態に関する知見は、アミロイド病Xは勿論のこと、別のアミロイド病研究にもインパクトが大きい。異なるアミロイド病は、原因タンパクの一次構造も異なるが、アミロイド線維への凝集過程は共有するメカニズムが多いためである。本研究で確立したアミロイドタンパクXの構造動態観察方法は、凝集阻害作用のあるとされる薬剤が凝集のどの反応過程を阻害するか検証することに利用できる。