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Structure and function of V. parahaemolyticus VepA and C. perfringens BEC

Research Project

Project/Area Number 17H04076
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Bacteriology (including mycology)
Research InstitutionOsaka University

Principal Investigator

Iida Tetsuya  大阪大学, 微生物病研究所, 教授 (90221746)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2019: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2017: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Keywords腸炎ビブリオ / ウェルシュ菌 / 毒素 / 結晶解析 / レセプター / エフェクター / 細菌 / 感染症
Outline of Final Research Achievements

In this study, the X-ray crystal structures of VepA and BEC, which are the major virulence factors of Vibrio parahaemolyticus and BEC-producing Clostridium perfringens, respectively, were analyzed to understand the mechanism of activity expression by the effector/toxin. For VepA, the structure of the complex with the chaperone VecA could be determined. Regarding BEC, X-ray crystal structures of apo-type and NADH complex were obtained for BECa having enzymatic activity, and the substrate recognition mechanism was elucidated at the atomic level. In addition, we were able to obtain new knowledge about the action of BECb on target cells.

Academic Significance and Societal Importance of the Research Achievements

VepAのようにV-ATPaseに直接作用する病原因子というのはほとんど知られていない。この機構の解明は生化学的、細胞生物学的に興味あるテーマである。またV-ATPaseはがん細胞の転移など医学的に重要なさまざまな現象に関与しており、今後さらにVepAについての研究を進めることにより、疾患の治療などへの新しい示唆が得られる可能性がある。BECは、他の二成分毒素と異なり、標的細胞への結合に関与するb成分のみでも腸管毒性を有する毒素である。本研究により解明されたメカニズムを踏まえた新たな治療法の開発が期待される。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (3 results)

All 2019

All Presentation (3 results) (of which Int'l Joint Research: 1 results)

  • [Presentation] ウェルシュ菌由来二成分毒素BECのサブユニットa(BECa)の酵素反応機構2019

    • Author(s)
      上田賢吾、河原一樹、余野木伸哉、沖大也、松田重輝、児玉年央、飯田哲也、吉田卓也、大久保忠恭、中村昇太
    • Organizer
      第92回日本細菌学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ウェルシュ菌由来ADPリボシル化毒素の酵素反応に重要なARTTループの構造多形2019

    • Author(s)
      木本成美、河原一樹、上田賢吾、余野木伸哉、沖大也、松田重輝、児玉年央、飯田哲也、吉田卓也、大久保忠恭、中村昇太
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Structural analysis of the ADP-ribosylating component of BEC, the binary enterotoxin of Clostridium perfringens2019

    • Author(s)
      Kengo Ueda, Kazuki Kawahara, Shinya Yonogi, Hiroya Oki, Shigeaki Matsuda, Toshio Kodama, Tetsuya Iida, Takuya Yoshida, Tadayasu Ohkubo, Shota Nakamura
    • Organizer
      ASM Microbe 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2021-02-19  

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