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Structural basis for ubiquitin chain-mediated DNA damage responses

Research Project

Project/Area Number 24247014
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Structural biochemistry
Research InstitutionThe University of Tokyo

Principal Investigator

Fukai Shuya  東京大学, 放射光連携研究機構, 准教授 (10361792)

Project Period (FY) 2012-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥44,330,000 (Direct Cost: ¥34,100,000、Indirect Cost: ¥10,230,000)
Fiscal Year 2015: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
Fiscal Year 2014: ¥10,270,000 (Direct Cost: ¥7,900,000、Indirect Cost: ¥2,370,000)
Fiscal Year 2013: ¥10,140,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥2,340,000)
Fiscal Year 2012: ¥14,170,000 (Direct Cost: ¥10,900,000、Indirect Cost: ¥3,270,000)
Keywords分子認識 / DNA修復 / タンパク質複合体 / ユビキチン / X線結晶構造解析 / 構造生物学 / X線結晶構造解析
Outline of Final Research Achievements

Ubiquitin serves as a signaling molecule for regulation of protein degradation and other important cellular functions. In many cases, two or more ubiquitin molecules are tandemly linked through covalent bonding to function as polyubiquitin chains. In this research project, we determined three-dimensional structures of protein complexes that play important roles in synthesis, degradation and recognition of K63-linked polyubiquitin chains (K63 chains) for DNA double strand break (DSB) responses to elucidate mechanisms for the K63 chain-mediated regulation of the DSB responses at atomic resolution. Furthermore, we revealed the structure-function relationships through structure-guided mutational analyses at the molecular and cellular levels.

Report

(5 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (12 results)

All 2016 2015 2014 2013 2012

All Journal Article (6 results) (of which Peer Reviewed: 5 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (5 results) (of which Invited: 3 results) Book (1 results)

  • [Journal Article] Structural basis for ubiquitin recognition by ubiquitin-binding zinc finger of FAAP202015

    • Author(s)
      Toma, A, Takahashi, T. S., Sato, Y., Yamagata, A., Goto-Ito, S., Nakada, S., Fukuto, A., Horikoshi, Y., Tashiro, S., Fukai, S.
    • Journal Title

      PLoS One

      Volume: 10 Issue: 3 Pages: 1-15

    • DOI

      10.1371/journal.pone.0120887

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Structures of CYLD USP with Met1- or Lys63-linked diubiquitin reveal mechanisms for dual specificity2015

    • Author(s)
      Sato, Y., Goto, E., Shibata, Y., Kubota, Y., Yamagata, A., Goto-Ito, S., Kubota, K., Inoue, J., Takekawa, M., Tokunaga, F. and Fukai, S.
    • Journal Title

      Nat. Struct. Mol. Biol.

      Volume: 22 Issue: 3 Pages: 222-229

    • DOI

      10.1038/nsmb.2970

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Core structures of ubiquitin dictate its dynamics and function2014

    • Author(s)
      Fukai, S.
    • Journal Title

      Journal of Molecular Biology

      Volume: 426 Issue: 7 Pages: 1367-1369

    • DOI

      10.1016/j.jmb.2013.12.008

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Get1 stabilizes an open dimer conformation of get3 ATPase by binding two distinct interfaces.2012

    • Author(s)
      Kubota K, Yamagata A, Sato Y, Goto-Ito S, Fukai S.
    • Journal Title

      J Mol Biol.

      Volume: 422(3) Issue: 3 Pages: 366-75

    • DOI

      10.1016/j.jmb.2012.05.045

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular basis of Lys-63-linked polyubiquitination inhibition by the interaction between human deubiquitinating enzyme OTUB1 and ubiquitin-conjugating enzyme UBC13.2012

    • Author(s)
      Sato Y, Yamagata A, Goto-Ito S, Kubota K, Miyamoto R, Nakada S, Fukai S.
    • Journal Title

      J Biol Chem.

      Volume: 287(31) Issue: 31 Pages: 25860-8

    • DOI

      10.1074/jbc.m112.364752

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ポリユビキチン鎖選択的結合による細胞機能制御2012

    • Author(s)
      佐藤裕介,深井周也
    • Journal Title

      生化学

      Volume: 84 Pages: 776-779

    • NAID

      10031122383

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] 化学的なユビキチン鎖合成のための試料調製法の探索2015

    • Author(s)
      中村美紅
    • Organizer
      BMB2015
    • Place of Presentation
      神戸ポートアイランド(兵庫県・神戸市)
    • Year and Date
      2015-12-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] ユビキチン鎖による炎症シグナル制御の構造基盤2014

    • Author(s)
      深井 周也
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2014-10-15
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 中程度の分解能での結晶構造解析2014

    • Author(s)
      深井 周也
    • Organizer
      第14回日本蛋白質科学会年会
    • Place of Presentation
      ワークピア横浜
    • Year and Date
      2014-06-27
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Structural basis for selective cleavage of M1- and K63-linked polyubiquitin chains by a CYLD deubiquitinase2013

    • Author(s)
      Shuya Fukai, Yusuke Sato
    • Organizer
      Cold Spring Harbor Laboratory 2013 meeting - The Ubiquitin Family
    • Place of Presentation
      Cold Spring Harbor Laboratory, 米国
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Structural basis for recognition of ubiquitin by UMI domain of RNF1682013

    • Author(s)
      Yusuke Sato, Aya Toma, Shuya Fukai
    • Organizer
      Cold Spring Harbor Laboratory 2013 meeting - The Ubiquitin Family
    • Place of Presentation
      Cold Spring Harbor Laboratory, 米国
    • Related Report
      2013 Annual Research Report
  • [Book] Advanced Methods in Structural Biology (Springer Protocols Handbooks)2016

    • Author(s)
      Shuya Fukai
    • Total Pages
      290
    • Publisher
      Springer
    • Related Report
      2015 Annual Research Report

URL: 

Published: 2013-05-15   Modified: 2019-07-29  

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