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Molecular mechanism of heme-regulated inhibitor (HRI) under stress conditions

Research Project

Project/Area Number 26340041
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Risk sciences of radiation and chemicals
Research InstitutionFukushima Medical University

Principal Investigator

Igarashi Jotaro  福島県立医科大学, 医学部, 准教授 (80375162)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsヘム / X線結晶構造解析 / 結晶構造解析 / グロビン / ヒ素 / ヘム調節インヒビター / タンパク質間相互作用
Outline of Final Research Achievements

Heme-regulated eukaryotic initiation factor 2α (eIF2α) kinase (HRI), functions in response to heme concentration. Under stress conditions, HRI forms stress granules and down-regulates protein synthesis. The molecular mechanism of HRI remained to be established. In the present study, we demonstrate that HRI degradation is inhibited by bortezomib in cultured cells. Using pull-down assay, the interaction between HRI and OGFOD1 are observed. Furthermore, to solve the crystal structure of HRI, insect cell expression systems are constructed.
In addition, we also elucidate the mechanism of ligand recognition of DgcO from Escherichia coli. DgcO, which is also known as YddV or DosC, consists of globin domain, middle domain, and diguanylate cyclase domain. We solved the crystal structure of globin domain of DgcO in the presence of various ligands.

Report

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

    (12 results)

All 2016 2015 2014 Other

All Presentation (9 results) (of which Int'l Joint Research: 3 results) Remarks (3 results)

  • [Presentation] Hoki myoglobin with unusual autoxidation behavior: Comparative analysis of native protein and H60V mutant2016

    • Author(s)
      Kobayashi, G., Igarashi, J., Rei, M., Nishiyama, N., Mizuguchi, T., Matsuoka, A.
    • Organizer
      The 22nd International Congress of Zoology and the 87th meeting of Zoological Society of Japan
    • Place of Presentation
      宜野湾
    • Year and Date
      2016-11-17
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 酸素センサータンパク質YddVのリガンド識別機構と活性調節2016

    • Author(s)
      五十嵐城太郎, 菊池亨, 松岡有樹
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台
    • Year and Date
      2016-09-27
    • Related Report
      2016 Annual Research Report
  • [Presentation] Ligand sensing mechanism of globin domain of a heme-based oxygen-sensor enzyme, YddV, from Escherichia coli.2016

    • Author(s)
      Igarashi, J., Kikuchi, T., Matsuoka, A.
    • Organizer
      The 19th International Conference on Oxygen Binding and Sensing Proteins
    • Place of Presentation
      Hamburg, Germany
    • Year and Date
      2016-09-13
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 酸素センサータンパク質 YddV のグロビンドメインの構造解析2016

    • Author(s)
      五十嵐城太郎, 松岡有樹
    • Organizer
      日本動物学会平成28年度東北支部大会
    • Place of Presentation
      福島
    • Year and Date
      2016-07-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] 酸素センサータンパク質YddVのグロビンドメインの構造解析2015

    • Author(s)
      五十嵐城太郎, 菊池亨, 松岡有樹
    • Organizer
      第38回日本分子生物学会年会・第88回日本生化学会大会合同大会(BMB2015)
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] Crystal structure of isolated heme-bound globin domain of a heme-based oxygen-sensor, YddV, from Escherichia coli.2015

    • Author(s)
      Igarashi, J., Kikuchi, T., and Matsuoka, A.
    • Organizer
      The 53rd Annual Meeting of the Biophysical Society of Japan
    • Place of Presentation
      Kanazawa, Japan
    • Year and Date
      2015-09-13
    • Related Report
      2015 Research-status Report
  • [Presentation] Stability properties of fish myoglobin from hoki (Macruronus magellanicus)2015

    • Author(s)
      Kobayashi, G., Nishiyama, N., Endo, Y., Mizuguchi, T., Igarashi, J., and Matsuoka, A.
    • Organizer
      The 9th International Congress of Comparative Physiology and Biochemistry
    • Place of Presentation
      Krakow, Poland
    • Year and Date
      2015-08-23
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 酸素センサー酵素Ec DOSのM30A変異体における構造変化2014

    • Author(s)
      五十嵐城太郎,清水透
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      京都
    • Year and Date
      2014-10-17
    • Related Report
      2014 Research-status Report
  • [Presentation] 大腸菌で発現させたホキ・ミオグロビンの分子特性2014

    • Author(s)
      小林元,遠藤優希,五十嵐城太郎,西山学即,水口亨,松岡有樹
    • Organizer
      平成26年度日本水産学会秋季大会
    • Place of Presentation
      福岡
    • Year and Date
      2014-09-20
    • Related Report
      2014 Research-status Report
  • [Remarks] 福島県立医科大学研究者データベース 研究者詳細-五十嵐 城太郎

    • URL

      http://www.fmu.ac.jp/kenkyu/html/1215_ja.html

    • Related Report
      2016 Annual Research Report
  • [Remarks] 福島県立医科大学 医学部医学科 自然科学講座(分子細胞生物学分野) 五十嵐 城太郎

    • URL

      http://www.fmu.ac.jp/kenkyu/Profiles/45/0004441/profile.html

    • Related Report
      2015 Research-status Report
  • [Remarks] 福島県立医科大学研究者データベース

    • URL

      http://www.fmu.ac.jp/kenkyu/Profiles/45/0004441/profile.html

    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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