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Structural elucidation of dioxin recognition by aryl hydrocarbon receptor

Research Project

Project/Area Number 15K14471
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Functional biochemistry
Research InstitutionThe University of Tokyo

Principal Investigator

Ohto Umeharu  東京大学, 大学院薬学系研究科(薬学部), 准教授 (90451856)

Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsダイオキシン / 環境ホルモン / 構造生物学 / X線結晶構造解析 / X線結晶解析
Outline of Final Research Achievements

We conducted the structural biology of aryl hydrocarbon receptor (AhR), known as dioxin receptor. We tried to prepare the pre-nuclear translocation complex of AhR but it was not successful. We conducted the crystallization of the AhR inhibitory complex, AhRR/ARNT complex, and determined its crystal structure. To obtain the structural information of the AhR transcriptional activation complex, AhR/ARNT complex, we tried to prepare AhR/ARNT complex derived from various organism species, and expressed and purified various mutants of AhR/ARNT.

Report

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

    (23 results)

All 2017 2016 2015 Other

All Int'l Joint Research (2 results) Journal Article (10 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 10 results,  Acknowledgement Compliant: 7 results,  Open Access: 3 results) Presentation (10 results) (of which Int'l Joint Research: 3 results,  Invited: 2 results) Remarks (1 results)

  • [Int'l Joint Research] ミネソタ大/コロラド大(米国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] ミネソタ大学/カンザス大学(米国)

    • Related Report
      2015 Research-status Report
  • [Journal Article] The crystal structure of mouse LC3B in complex with the FYCO1 LIR reveals the importance of the flanking region of the LIR motif.2017

    • Author(s)
      Sakurai S, Tomita T, Shimizu T, Ohto U
    • Journal Title

      Acta Crystallographica Section F

      Volume: 73 Issue: 3 Pages: 130-137

    • DOI

      10.1107/s2053230x17001911

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Emerging roles of the processing of nucleic acids and Toll-like receptors in innate immune responses to nucleic acids2017

    • Author(s)
      Miyake K, Shibata T, Ohto U, Shimizu T
    • Journal Title

      J Leukoc Biol

      Volume: 101 Issue: 1 Pages: 135-142

    • DOI

      10.1189/jlb.4mr0316-108r

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Structural Analysis Reveals that Toll-like Receptor 7 Is a Dual Receptor for Guanosine and Single-Stranded RNA2016

    • Author(s)
      Zhang Z, Ohto U, Shibata T, Krayukhina E, Taoka M, Yamauchi Y, Tanji H, Isobe T, Uchiyama S, Miyake K, Shimizu T
    • Journal Title

      Immunity

      Volume: 45 Issue: 4 Pages: 737-748

    • DOI

      10.1016/j.immuni.2016.09.011

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Crystal structure of NOD2 and its implications in human disease.2016

    • Author(s)
      Maekawa S, Ohto U, Shibata T, Miyake K, Shimizu T
    • Journal Title

      Nat Commun

      Volume: 7 Issue: 1 Pages: 11813-11813

    • DOI

      10.1038/ncomms11813

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of a Human Toll-Like Receptor (TLR) 8-Specific Agonist and a Functional Pan-TLR Inhibitor in 2-Aminoimidazoles.2016

    • Author(s)
      Beesu, M., Caruso, G., Salyer, A. C., Shukla, N. M., Khetani, K. K., Smith, L. J., Fox, L. M., Tanji, H., Ohto, U., Shimizu, T., & David, S. A.
    • Journal Title

      J. Med. Chem.

      Volume: 59 Issue: 7 Pages: 3311-3330

    • DOI

      10.1021/acs.jmedchem.6b00023

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Autoinhibition and relief mechanism by the proteolytic processing of Toll-like receptor 8.2016

    • Author(s)
      Tanji, H., Ohto, U., Motoi, Y., Shibata, T., Miyake, K., & Shimizu, T.
    • Journal Title

      Proc. Natl. Acad. Sci. U S A

      Volume: 113 Issue: 11 Pages: 3012-3017

    • DOI

      10.1073/pnas.1516000113

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Eritoran inhibits S100A8-mediated TLR4/MD-2 activation and tumor growth by changing the immune microenvironment.2016

    • Author(s)
      Deguchi A, Tomita T, Ohto U, Takemura K, Kitao A, Akashi-Takamura, S, Miyake K, and Maru Y.
    • Journal Title

      Oncogene

      Volume: 35 Issue: 11 Pages: 1445-1456

    • DOI

      10.1038/onc.2015.211

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Structure-based Design of Human TLR8-specific Agonists with Augmented Potency and Adjuvanticity.2015

    • Author(s)
      Beesu, M., Caruso, G., Salyer, A., Khetani, K., Sil, D., Weerasinghe, M., Tanji, H., Ohto, U., Shimizu, T., & David, S. A.
    • Journal Title

      J. Med. Chem.

      Volume: 58 Issue: 19 Pages: 7833-7849

    • DOI

      10.1021/acs.jmedchem.5b01087

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] The Imidazoquinoline Toll-Like Receptor-7/8 Agonist Hybrid-2 Potently Induces Cytokine Production by Human Newborn and Adult Leukocytes.2015

    • Author(s)
      Ganapathi, L., Van Haren, S., Dowling, D. J., Bergelson, I., Shukla, N. M., Malladi, S. S., Balakrishna, R., Tanji, H., Ohto, U., Shimizu, T., David, S. A., & Levy, O.
    • Journal Title

      PLoS One

      Volume: 10 Issue: 8 Pages: 0134640-0134640

    • DOI

      10.1371/journal.pone.0134640

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Structure of human Roquin-2 and its complex with constitutive-decay element RNA.2015

    • Author(s)
      Sakurai, S., Ohto, U., & Shimizu, T.
    • Journal Title

      Acta Crystallogr. Sect. F

      Volume: 71 Issue: 8 Pages: 1048-1054

    • DOI

      10.1107/s2053230x15011887

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Structures of nucleic acids sensing Toll-like receptors2016

    • Author(s)
      Umeharu Ohto and Toshiyuki Shimizu
    • Organizer
      The 45th annual meeting of the Japanese Society for Immunology (JSI)(
    • Place of Presentation
      沖縄コンベンションセンター(沖縄、宜野湾)
    • Year and Date
      2016-12-05
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Structural studies of innate immune RNA receptor human TLR82016

    • Author(s)
      Hiromi Tanji, Umeharu Ohto, Toshiyuki Shimizu
    • Organizer
      14th Conference of the Asian Crystallographic Association
    • Place of Presentation
      Hanoi, Vietnam
    • Year and Date
      2016-12-04
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 自然免疫受容体 TLR7 の構造学的研究2016

    • Author(s)
      張志寛、大戸梅治、清水敏之
    • Organizer
      第16回日本蛋白質科学会年会
    • Place of Presentation
      福岡国際会議場(福岡、博多)
    • Year and Date
      2016-06-07
    • Related Report
      2016 Annual Research Report
  • [Presentation] 核酸認識Toll様受容体によるリガンド認識とシグナル伝達の構造基盤2015

    • Author(s)
      大戸梅治、清水敏之
    • Organizer
      BMB2015 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
    • Place of Presentation
      神戸ポートアイランド(神戸)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] mRNA分解に関与するタンパク質Roquin-2とRNA複合体のX線結晶構造解析2015

    • Author(s)
      櫻井駿也、大戸梅治、清水敏之
    • Organizer
      平成27年度日本結晶学会
    • Place of Presentation
      大阪府立大学(大阪)
    • Year and Date
      2015-10-17
    • Related Report
      2015 Research-status Report
  • [Presentation] Structural studies of single-stranded RNA receptor TLR82015

    • Author(s)
      Hiromi Tanji, Umeharu Ohto, Takuma Shibaga, Kensuke Miyake, Toshiyuki Shimizu
    • Organizer
      Toll meeting 2015
    • Place of Presentation
      Marbella, Spain
    • Year and Date
      2015-09-30
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Crystallographic analyses of Toll-like receptor 9 recognizing CpG DNA2015

    • Author(s)
      U. Ohto, T. Shibata, H. Tanji, H. Ishida, E. Krayukhina, S. Uchiyama, K. Miyake, and T. Shimizu
    • Organizer
      Toll meeting 2015
    • Place of Presentation
      Marbella, Spain
    • Year and Date
      2015-09-30
    • Related Report
      2015 Research-status Report
  • [Presentation] Ligand recognition and signal transduction by Toll-like receptor2015

    • Author(s)
      Umeharu Ohto
    • Organizer
      第53回日本生物物理学会
    • Place of Presentation
      金沢大学(金沢)
    • Year and Date
      2015-09-13
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 自然免疫受容体NOD2の構造学的研究2015

    • Author(s)
      前川早貴子、大戸梅治、清水敏之
    • Organizer
      第15回日本蛋白質科学会年会
    • Place of Presentation
      あわぎんホール(徳島)
    • Year and Date
      2015-06-24
    • Related Report
      2015 Research-status Report
  • [Presentation] 自然免疫系一本鎖RNA受容体TLR8の構造基盤2015

    • Author(s)
      丹治裕美、大戸梅治、柴田琢磨、田岡万悟、山内芳雄、礒邉俊明、三宅健介、清水敏之
    • Organizer
      第15回日本蛋白質科学会年会
    • Place of Presentation
      あわぎんホール(徳島)
    • Year and Date
      2015-06-24
    • Related Report
      2015 Research-status Report
  • [Remarks] 研究室ホームページ

    • URL

      http://www.f.u-tokyo.ac.jp/~kouzou/index.html

    • Related Report
      2016 Annual Research Report 2015 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2022-02-16  

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