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NMR study of the formation and dissolution mechanisms of Sup35 amyloid fibrils.

Research Project

Project/Area Number 23770193
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Biophysics
Research InstitutionThe Institute of Physical and Chemical Research

Principal Investigator

OHHASHI Yumiko  独立行政法人理化学研究所, 脳科学総合研究センター, 研究員 (10422669)

Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsアミロイド / 核磁気共鳴法 / 構造多形 / Sup35 / 天然変性蛋白質 / 部分構造 / 揺らぎ / 核磁気共鳴 / タンパク質
Research Abstract

Protein aggregates (amyloid) are common pathological feature of most neurodegenerative diseases. In this study, I investigated the molecular mechanism controlling of determination of amyloid structural polymorphism which affects the clinical state of such diseases, using a yeast prion protein, Sup35. From measurements of several NMR methods focusing on the Sup35 structural fluctuation and local conformation, I found two amyloid initiation sites on Sup35 sequence. Thus, it was conceivable that amyloid structural polymorphism arises from the competition of these two sites. Next, I found the relatively compact local conformation in a part of WT Sup35NM. This result exhibited that the one initiation site is included in this compact area, so another site is advantageous in WT amyloid formation. In conclusion, it was suggested that amyloid structural polymorphism is induced by the destruction of local conformation by amino acid substitution.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (10 results)

All 2013 2012 2011

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (9 results) (of which Invited: 2 results)

  • [Journal Article] Radically different amyloid conformations dictate the seeding specificity of a chimeric Sup35 prion2011

    • Author(s)
      Foo CK, Ohhashi Y, Kelly MJ, Tanaka M, and Weissman JS
    • Journal Title

      J Mol Biol

      Volume: 408(1) Pages: 1-8

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Presentation] 酵母プリオンSup35を用いたアミロイド構造多形形成メカニズムの解明2013

    • Author(s)
      大橋祐美子、山口芳樹、鎌足雄司、花島慎弥、桑田一夫、田中元雅
    • Organizer
      第13回日本蛋白質科学会年会
    • Place of Presentation
      鳥取市とりぎん文化会館
    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Invited
  • [Presentation] 酵母プリオンSup35を用いたアミロイド構造多形形成メカニズムの解明2013

    • Author(s)
      大橋祐美子
    • Organizer
      第13回日本蛋白質科学会
    • Place of Presentation
      鳥取市 とりぎん文化会館
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] アミロイド構造の決定におけるタンパク質揺らぎの役割の解析2012

    • Author(s)
      大橋祐美子、田中元雅
    • Organizer
      第50回日本生物物理学会年会
    • Place of Presentation
      名古屋市・名古屋大学東山キャンパス
    • Related Report
      2013 Final Research Report
  • [Presentation] Protein fluctuation in monomer determines prion strain conformations2012

    • Author(s)
      Yumiko Ohhashi and Motomasa Tanaka
    • Organizer
      Asian Pacific Prion Symposium 2012
    • Place of Presentation
      Pacifico Yokohama, Japan
    • Related Report
      2013 Final Research Report
  • [Presentation] アミロイド構造の決定におけるタンパク質揺らぎの役割の解析2012

    • Author(s)
      大橋祐美子、山口芳樹、鎌足雄司、花島慎弥、桑田一夫、田中元雅
    • Organizer
      第50回日本生物物理学会年会
    • Place of Presentation
      名古屋大学東山キャンパス
    • Related Report
      2012 Research-status Report
  • [Presentation] Protein fluctuation in monomer determines prion strain conformations2012

    • Author(s)
      大橋祐美子、田中元雅
    • Organizer
      Asian Pacific Prion Symposium 2012
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] Role of protein fluctuation in determination of amyloid conformation2011

    • Author(s)
      Yumiko Ohhashii and Motomasa Tanaka
    • Organizer
      The ssInternational symposium on Nuclear Magnetic Resonance 2011
    • Place of Presentation
      OSANBASHI Hall, Yokohama, Japan
    • Related Report
      2013 Final Research Report
  • [Presentation] Structural basis for the diversity of prion strain conformations2011

    • Author(s)
      Yumiko Ohhashi and Motomasa Tanaka
    • Organizer
      Asian Pacific Prion Symposium 2011
    • Place of Presentation
      Hotel Marroad Karuizawa, Nagano, Japan
    • Related Report
      2013 Final Research Report
  • [Presentation] Role of protein fluctuation in determination of amyloid conformation.2011

    • Author(s)
      大橋祐美子、田中元雅
    • Organizer
      The International symposium on Nuclear Magnetic Resonance 2011
    • Place of Presentation
      横浜、大さん橋ホール
    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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