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The structural analysis of beta2-microglobulin amyloid fibril

Research Project

Project/Area Number 17K15074
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Structural biochemistry
Research InstitutionOsaka 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
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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 / β2ミクログロブリン / 構造解析 / β2ミクログロブリン / β2-ミクログロブリン
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.

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。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (3 results)

All 2019 2018

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 1 results) Book (1 results)

  • [Journal Article] Aggregation-phase diagrams of β2-microglobulin reveal temperature and salt effects on competitive formation of amyloids versus amorphous aggregates2018

    • Author(s)
      Masayuki Adachi, Masahiro Noji, Masatomo So, Kenji Sasahara, Jozsef Kardos, Hironobu Naiki, Yuji Goto
    • Journal Title

      Journal of Biological Chemistry

      Volume: 293 Issue: 38 Pages: 14775-14785

    • DOI

      10.1074/jbc.ra118.004683

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Heat-induced aggregation of hen ovalbumin suggests a key factor responsible for serpin polymerization.2018

    • Author(s)
      Noji, M., So, M., Yamaguchi, K., Hojo, H., Onda, .M., Akazawa-Ogawa, Y., Hagihara, Y. and Goto, Y.
    • Journal Title

      Biochemistry

      Volume: 57(37) Issue: 37 Pages: 5415-5426

    • DOI

      10.1021/acs.biochem.8b00619

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Book] タンパク質のアモルファス凝集と溶解性2019

    • Author(s)
      宗正智、後藤祐児
    • Total Pages
      283
    • Publisher
      シーエムシー出版
    • ISBN
      9784781313979
    • Related Report
      2018 Annual Research Report

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Published: 2017-04-28   Modified: 2020-03-30  

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