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Structural analyses of bacterial effectors and their mechanisms of infection

Research Project

Project/Area Number 24370049
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Structural biochemistry
Research InstitutionUniversity of Hyogo

Principal Investigator

MIZUSHIMA TSUNEHIRO  兵庫県立大学, 生命理学研究科, 教授 (90362269)

Co-Investigator(Renkei-kenkyūsha) KIM Minsoo  東京大学, 医科学研究所, 特任准教授 (50466835)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000)
Fiscal Year 2014: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2012: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000)
Keywordsエフェクター / 赤痢菌 / X線結晶構造解析 / ユビキチン経路 / 蛋白質 / 細菌 / エフェクタータンパク質 / 複合体構造 / OspI
Outline of Final Research Achievements

Pathogenic bacteria such as Shigella, EPEC, and Salmonella deliver a variety of virulence factors, called effectors, into host cells via the type III secretion system. These effectors mimic or hijack host proteins and modulate host signaling pathways to promote bacterial infection. OspI, a Shigella flexneri effector, is a glutamine deamidase that selectively deamidates the glutamine residue at position 100 in Ubc13 to a glutamic acid residue. This modification inhibits the E2 ubiquitin conjugating activity, which is required for TRAF6 activation. To elucidate the molecular mechanisms of OspI, we determined the crystal structures of OspI mutant and its complex with Ubc13. These structures provide the substrate recognition and catalytic mechanism.

Report

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

    (16 results)

All 2015 2014 2013 2012

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (12 results) (of which Invited: 1 results)

  • [Journal Article] Bacterial Effectors and Their Functions in the Ubiquitin-Proteasome System: Insight from the Modes of Substrate Recognition2014

    • Author(s)
      Kim M et. al
    • Journal Title

      Cells

      Volume: 3 Issue: 3 Pages: 848-864

    • DOI

      10.3390/cells3030848

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Structural basis for the recognition of Ubcl3 by the Shigell a flexneri effector OspI2013

    • Author(s)
      Nishide A, et. al
    • Journal Title

      J Mol Bio.

      Volume: 425 Issue: 15 Pages: 2623-2631

    • DOI

      10.1016/j.jmb.2013.02.037

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Shigella OspC3 effector inhibits Cspase-4, antagonizes inflammatory cell death, and promotes epithelial infection2013

    • Author(s)
      Kobayashi T, et. al
    • Journal Title

      Cell Host Microbe

      Volume: 13 Issue: 5 Pages: 570-583

    • DOI

      10.1016/j.chom.2013.04.012

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structural basis for the recognition of Ubcl3 by the Shigella flexneri effector OspI.2013

    • Author(s)
      Nishide A, Kim M, Takagi K, Himeno A, Sanada T, Sasakawa C, Mizushima T.
    • Journal Title

      Journal of Molecular Biology

      Volume: (in press)

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] Structural Basis for the Recognition of Ubc13 by the Shigella flexneri Effector OspI2015

    • Author(s)
      Nishide, A., Kim, M., Takagi, K., Himeno, A., Sanada, T., Sasakawa, C., Mizushima, T.
    • Organizer
      The Annual Evaluation Conference of the Leading Program, University of Hyogo
    • Place of Presentation
      先端科学技術支援センター (兵庫・赤穂郡上郡町)
    • Year and Date
      2015-03-16 – 2015-03-17
    • Related Report
      2014 Annual Research Report
  • [Presentation] Structure and substrate recognition mechanism of IpaH9.8 LRR2014

    • Author(s)
      Takagi, K., Nishide, A., Mizushima, T.
    • Organizer
      Symposium for young ubiquitin researchers in Japan “New Era in the Ubiquitin Research
    • Place of Presentation
      国際高等研究所(京都・木津川市)
    • Year and Date
      2014-11-11 – 2014-11-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] Structural Basis for the Recognition of Ubc13 by the Shigella flexneri Effector OspI2014

    • Author(s)
      Nishide, A., Kim, M., Takagi, K., Himeno, A., Sanada, T., Sasakawa, C., Mizushima, T.
    • Organizer
      Symposium for young ubiquitin researchers in Japan “New Era in the Ubiquitin Research
    • Place of Presentation
      国際高等研究所(京都・木津川市)
    • Year and Date
      2014-11-11 – 2014-11-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] 赤痢菌エフェクターIpaH9.8基質認識ドメインのX線結晶構造解析2014

    • Author(s)
      高木賢治、水島恒裕
    • Organizer
      日本結晶学会
    • Place of Presentation
      東京大学(東京)
    • Year and Date
      2014-11-01 – 2014-11-03
    • Related Report
      2014 Annual Research Report
  • [Presentation] Structural analyses of bacterial effectors and their mechanisms of infection in the ubiquitin-proteasome system2014

    • Author(s)
      Mizushima T.
    • Organizer
      2nd International Picobiology Institute Symposium Development & Destruction
    • Place of Presentation
      先端科学技術支援センター (兵庫・赤穂郡上郡町)
    • Year and Date
      2014-10-09 – 2014-10-10
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 赤痢菌エフェクターOspIの結晶構造解析による感染機構の解明2014

    • Author(s)
      西出旭、水島恒裕
    • Organizer
      兵庫県立大学 知の交流シンポジウム
    • Place of Presentation
      姫路商工会議所 (兵庫・姫路市)
    • Year and Date
      2014-09-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] OspI-Ubc13複合体構造解析による赤痢菌エフェクタータンパク質のE2酵素認識機構2013

    • Author(s)
      西出旭、Minsoo Kim、高木賢治、真田貴人、笹川千尋、水島恒裕
    • Organizer
      第13回日本蛋白質科学会年会
    • Place of Presentation
      とりぎん文化会館 (鳥取)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Structural basis for the recognition of Ubc13 by the Shigella flexneri effector OspI2013

    • Author(s)
      Nishide A., Kim M., Takagi K., Himeno A., Sanada T., Sasakawa C., Mizushima T.
    • Organizer
      The 35th Naito Conference
    • Place of Presentation
      シャトレーゼガトーキングダム(北海道)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 赤痢菌エフェクタータンパク質OspI-Ubc13複合体結晶構造解析による機能解析2013

    • Author(s)
      西出 旭,Minsoo Kim,高木 賢治,真田 真人,笹川 千尋,水島 恒裕
    • Organizer
      新学術領域『ユビキチンネオバイオロジー』第2回領域会議
    • Place of Presentation
      熱海ニューフジヤホテル (静岡)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 脱アミド化Ubc13の構造解析による赤痢菌感染機構の考察2013

    • Author(s)
      高木賢治 西出旭、Kim Minsoo、笹川千尋、水島恒裕
    • Organizer
      新学術領域『ユビキチンネオバイオロジー』第2回領域会議
    • Place of Presentation
      熱海ニューフジヤホテル (静岡)
    • Related Report
      2013 Annual Research Report
  • [Presentation] プロテアソーム複合体構造とシャペロンによる形成機構2012

    • Author(s)
      水島恒裕
    • Organizer
      第85回 日本生化学会大会
    • Place of Presentation
      福岡国際会議場(福岡)(招待講演)
    • Year and Date
      2012-12-14
    • Related Report
      2012 Annual Research Report
  • [Presentation] 赤痢菌エフェクタータンパク質OspI 活性中心の構造解析2012

    • Author(s)
      西出旭、高木賢治、Minsoo Kim、真田貴人、笹川千尋、水島恒裕
    • Organizer
      第12回 日本蛋白質科学会年会
    • Place of Presentation
      名古屋国際会議場(愛知)
    • Year and Date
      2012-06-20
    • Related Report
      2012 Annual Research Report

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Published: 2012-04-24   Modified: 2021-04-07  

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