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Functional analysis of ER-60, an ER chaperone by gene mamipulation and crystal structure analysis

Research Project

Project/Area Number 25292070
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Food science
Research InstitutionKyoto University

Principal Investigator

Reiko Urade  京都大学, (連合)農学研究科(研究院), 教授 (90167289)

Co-Investigator(Kenkyū-buntansha) 裏出 良博  筑波大学, 学内共同利用施設等, 教授 (10201360)
Co-Investigator(Renkei-kenkyūsha) Lazarus Michael  筑波大学, 国際統合睡眠医科学研究機構, 若手フェロー (80469650)
Cherasse Yoan  筑波大学, 国際統合睡眠医科学研究機構, 研究員 (60544319)
Nagata Nanae  筑波大学, 国際統合睡眠医科学研究機構, 研究員 (80390805)
Research Collaborator Higashino Yuki  京都大学, 大学院農学研究科, 技術職員
Natsusaki Motonori  京都大学, 大学院農学研究科, 研究員
Okuda Aya  京都大学, 大学院農学研究科・学術振興会, 特別研究員PD
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2015: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2014: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2013: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Keywordsアミロイドβペプチド / 小胞体 / 分子シャペロン / 結晶構造解析 / アルツハイマー病 / タンパク質結晶構造解析 / 酵素 / ノックアウトマウス / ER-60
Outline of Final Research Achievements

The project was performed to clarify the relationship between Alzheimer’s dementia and a molecular chaperon located in the endoplasmic reticulum, ER-60. We demonstrated that ER-60 has protective effects against toxicity of amyloid beta peptides by using brain neuron-specific ER-60 knockout mice. The function is exerted through inhibition of polymerization of amyloid beta peptides by b-b' domain of ER-60. The amino acid residues essential for
binding to amyloid beta peptides were identified by X-ray structural analysis of a complex of the b-b’ fragment of ER-60 and amyloid beta peptide. In addition, it was suggested that amyloid beta peptides bind to b-b' domain in a flexible manners.

Report

(4 results)
  • 2016 Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (5 results)

All 2017 2016 2014 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (3 results) (of which Invited: 3 results)

  • [Journal Article] Identification and characterization of GmPDIL7, a soybean ER membrane-bound protein disulfide isomerase family protein2017

    • Author(s)
      Okuda A, Matsusaki M, Masuda T, Urade R.
    • Journal Title

      FEBS Journal

      Volume: 284 Issue: 3 Pages: 414-428

    • DOI

      10.1111/febs.13984

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cooperative Protein Folding by Two Protein Thiol Disulfide Oxidoreductases and ERO1 in Soybean2016

    • Author(s)
      Matsusaki M, Okuda A, Masuda T, Koishihara K, Mita R, Iwasaki K, Hara K, Naruo Y, Hirose A, Tsuchi Y, Urade R
    • Journal Title

      Plant Physiology

      Volume: 170 Issue: 2 Pages: 774-774

    • DOI

      10.1104/pp.15.01781

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Protective Effects of ER-60 against Cytotoxicity of Amyloid β Peptide2016

    • Author(s)
      Reiko Urade
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台国際会議場
    • Year and Date
      2016-09-25
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] ER-60のアミロイドβペプチド細胞毒性抑制機構2014

    • Author(s)
      裏出 令子
    • Organizer
      第14回 日本蛋白質科学会
    • Place of Presentation
      ワークピア横浜
    • Year and Date
      2014-06-26
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 小胞体ER-60による

    • Author(s)
      裏出令子
    • Organizer
      第7回レドックスイノベーションシンポジウム
    • Place of Presentation
      東京大学
    • Related Report
      2013 Annual Research Report
    • Invited

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Published: 2013-05-21   Modified: 2019-07-29  

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