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Understanding the molecular mechanism of co-translational oxidative folding in the ER

Research Project

Project/Area Number 17H06521
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field Biophysics
Research InstitutionKwansei Gakuin University (2018)
Tohoku University (2017)

Principal Investigator

Kanemura Shingo  関西学院大学, 理工学部, 助教 (50803178)

Project Period (FY) 2017-08-25 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords無細胞タンパク質合成系 / セミインタクト細胞 / PDIファミリー / ジスルフィド結合 / 新生鎖
Outline of Final Research Achievements

In order to provide structural insight into "the mechanism of how oxidative folding occurs co-translationally in the ER", I developed "a monitoring system regarding the reaction of disulfide bond formation of nascent polypeptides". The results indicated that a disulfide bond of the β2m nascent chain is formed in the lumen of the ER during the translation elongation, and disulfide bonds of prolactin, insulin, and BPTI nascent chain are post-translationally formed.

Academic Significance and Societal Importance of the Research Achievements

本研究によって、新生鎖のジスルフィド結合形成過程の観察に成功した。本成果は今後、インスリンや免疫グロブリンなどの生物学的、医学的にも重要なタンパク質の立体構造を構築する(フォールディング)機序の解明に繋がると期待できる。フォールディング機序の解明は、ミスフォールディングに起因する神経変性疾患などの予防や発症機構の解明にも繋がり、医学分野への貢献も大いに期待でき非常に意義深い。

Report

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

    (9 results)

All 2019 2018 2017 Other

All Int'l Joint Research (3 results) Journal Article (3 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (3 results)

  • [Int'l Joint Research] University of Glasgow(英国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] University of Utah(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] University of Glasgow(英国)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Protein Disulfide Isomerase family: from Proteostasis to Pathogenesis2019

    • Author(s)
      Matsusaki M.#, Kanemura S.#, Kinoshita M.#, Lee Y.H., Inaba K.*, and Okumura M.* (#equal contribution *corresponding authors)
    • Journal Title

      Biochim Biophys Acta-general subjects

      Volume: in press Issue: 2 Pages: 30080-30087

    • DOI

      10.1016/j.bbagen.2019.04.003

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dynamic assembly of protein disulfide isomerase in catalysis of oxidative folding2019

    • Author(s)
      Okumura Masaki、Noi Kentaro、Kanemura Shingo、Kinoshita Misaki、Saio Tomohide、Inoue Yuichi、Hikima Takaaki、Akiyama Shuji、Ogura Teru、Inaba Kenji
    • Journal Title

      Nature Chemical Biology

      Volume: 15 Issue: 5 Pages: 499-509

    • DOI

      10.1038/s41589-019-0268-8

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ero1-mediated reoxidation of PDI accelerates the folding of cone-snail toxins2018

    • Author(s)
      O'Brien H., Kanemura S., Okumura M., Baskin P., Bandyopadhyay P., Ellgaard L., Inaba K., and Safavi-Hemami H.*
    • Journal Title

      Int. J. Mol. Sci.

      Volume: 11 Issue: 11 Pages: 3418-3418

    • DOI

      10.3390/ijms19113418

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 小胞体内における新生鎖のジスルフィド結合形成機構の解明2019

    • Author(s)
      金村進吾
    • Organizer
      第19回日本蛋白質科学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 小胞体内腔における新生鎖のジスルフィド結合形成反応の解析2018

    • Author(s)
      金村進吾
    • Organizer
      第18回日本蛋白質科学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 小胞体内腔における新生ポリペプチド鎖のジスルフィド結合形成をモニタリングするシステムの開発2017

    • Author(s)
      金村進吾
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Annual Research Report

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Published: 2017-08-25   Modified: 2022-06-14  

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