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New Paradigm for molecular mechanism of amyloid formation and disaggregation

Research Project

Project/Area Number 15H04345
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Structural biochemistry
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Tanaka Motomasa  国立研究開発法人理化学研究所, 脳科学総合研究センター, チームリーダー (40321781)

Co-Investigator(Renkei-kenkyūsha) KUWATA Kazuo  岐阜大学, 連合創薬医療情報研究科, 教授 (00170142)
KONNO Hiroki  金沢大学, バイオAFM先端研究センター, 准教授 (80419267)
Research Collaborator NAKAGAWA Yoshiko  
Shen Chih-hao  
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000)
Fiscal Year 2017: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Keywordsアミロイド / 神経変性疾患 / 精神疾患 / タンパク質 / プリオン / シャペロン / 蛋白質 / 酵母プリオン / 脳神経疾患 / 分子シャペロン
Outline of Final Research Achievements

Self-propagating β-sheet-rich fibrillar protein aggregates, amyloid fibers, are often associated with cellular dysfunction and disease. Distinct amyloid conformations dictate different physiological consequences, such as cellular toxicity. However, the origin of the diversity of amyloid conformation remains unknown. Here, we suggest that altered conformational equilibrium in natively disordered monomeric proteins leads to the adaptation of alternate amyloid conformations that have different phenotypic effects. We performed a comprehensive high-resolution structural analysis of Sup35NM, an N-terminal fragment of the Sup35 yeast prion protein, and found that monomeric Sup35NM harbored latent local compact structures despite its overall disordered conformation. In addition, we found that the chaperone machinery has distinct remodeling activity to different prion strain conformations of Sup35.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (6 results)

All 2018 2016 Other

All Int'l Joint Research (1 results) Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (3 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Remarks (1 results)

  • [Int'l Joint Research] デュッセルドルフ大学 物理生物学研究所(ドイツ)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Molecular basis for diversification of yeast prion strain conformation2018

    • Author(s)
      Ohhashi Yumiko、Yamaguchi Yoshiki、Kurahashi Hiroshi、Kamatari Yuji O.、Sugiyama Shinju、Uluca Boran、Piechatzek Timo、Komi Yusuke、Shida Toshinobu、M?ller Henrik、Hanashima Shinya、Heise Henrike、Kuwata Kazuo、Tanaka Motomasa
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 115 Issue: 10 Pages: 2389-2394

    • DOI

      10.1073/pnas.1715483115

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Molecular basis for Hsp104-mediated prion propagation in yeast2016

    • Author(s)
      Yoshiko Nakagawa, Hideki Taguchi, Motomasa Tanaka
    • Organizer
      第54回日本生物物理学会大会
    • Place of Presentation
      つくば国際会議場
    • Year and Date
      2016-11-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] プリオン様タンパク質の感染性の本体とその生成分子機構の解明2016

    • Author(s)
      田中元雅、大橋祐美子、志田俊信
    • Organizer
      第21回日本神経感染症学会
    • Place of Presentation
      金沢東急ホテル
    • Year and Date
      2016-10-21
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Latent structural variation in a yeast prion monomer determines strain phenotypes2016

    • Author(s)
      Motomasa Tanaka, Yumiko Ohhashi, Yoshiki Yamaguchi, Yuji O. Kamatari, Kazuo Kuwata
    • Organizer
      PRION2016
    • Place of Presentation
      Hitotsubashi Hall, National Center of Sciences Building
    • Year and Date
      2016-05-10
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Remarks] アミロイド構造の多様性の原因解明

    • URL

      http://www.riken.jp/pr/press/2018/20180322_1/

    • Related Report
      2017 Annual Research Report

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Published: 2015-04-16   Modified: 2019-03-29  

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