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自然免疫系受容体による病原体認識機構の解明

Publicly Offered Research

Project AreaStructural basis of cell-signalling complexes mediating signal perception, transduction and responses
Project/Area Number 25121709
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionThe University of Tokyo

Principal Investigator

大戸 梅治  東京大学, 薬学研究科(研究院), 講師 (90451856)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
Fiscal Year 2014: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2013: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Keywords自然免疫 / X線結晶構造解析
Outline of Annual Research Achievements

自然免疫は微生物の感染に対する生体の初期防御反応である。微生物の構成成分はToll-like receptors (TLRs),NOD-like receptors (NLRs),RIG-I-like receptors (RLRs)などの受容体によって認識されることで様々な免疫応答を引き起こす。これら受容体は,様々な病気の治療薬のターゲットとして注目されている。本課題では,自然免疫系の受容体によるリガンド認識機構やシグナル伝達機構を主にX線結晶構造解析により明らかにすることを目的する。
1.核酸認識TLRs (TLR7,TLR8,TLR9)と核酸の複合体(抗ウイルス薬,ワクチン)
2.細胞内NLRs (Nod1,Nod2など)とリガンドの複合体(クローン病,アレルギー)
本年度は、1に関してはTLR8とRNA複合体の結晶構造解析に成功した。さらに、CpG DNAを認識するTLR9の構造解析にも成功した。
2に関してはNod1とNod2の大量調製法の検討を前年度に引き続き行った。その結果、高純度試料の調製に成功し、Nod2に関して構造解析可能な結晶を得ることができた。

Research Progress Status

26年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

26年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (15 results)

All 2015 2014 2013

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Acknowledgement Compliant: 4 results) Presentation (8 results) (of which Invited: 1 results)

  • [Journal Article] Toll-like receptor 8 senses degradation products of single-stranded RNA.2015

    • Author(s)
      Tanji H, Ohto U, Shibata T, Taoka M, Yamauchi Y, Isobe T, Miyake K,
    • Journal Title

      Nat Struct Mol Biol.

      Volume: 22 Issue: 2 Pages: 109-115

    • DOI

      10.1038/nsmb.2943

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Determinants of activity at human Toll-like receptors 7 and 8: quantitative structure-activity2014

    • Author(s)
      Yoo E, Salunke DB, Sil D, Guo X, Salyer AC, Hermanson AR, Kumar M,
    • Journal Title

      J Med Chem.

      Volume: 57 Issue: 19 Pages: 7955-7970

    • DOI

      10.1021/jm500744f

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Structural basis of pharmacological chaperoning for human β-galactosidase2014

    • Author(s)
      Suzuki H, et al.
    • Journal Title

      J. Biol. Chem.

      Volume: 289 Issue: 21 Pages: 14560-14568

    • DOI

      10.1074/jbc.m113.529529

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Structure-Based Design of Novel Human Toll-like Receptor 8 Agonists.2014

    • Author(s)
      Kokatla, H. P., Sil, D., Tanji, H., Ohto, U., Malladi, S. S., Fox, L. M., Shimizu, T., & David, S. A.
    • Journal Title

      ChemMedChem.

      Volume: 9 Issue: 4 Pages: 713-723

    • DOI

      10.1002/cmdc.201300573

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structure and function of toll-like receptor 8.2014

    • Author(s)
      Ohto, U., Tanji, H., & Shimizu, T.
    • Journal Title

      Microbes Infect.

      Volume: 16 Issue: 4 Pages: 273-282

    • DOI

      10.1016/j.micinf.2014.01.007

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impaired α-TTP-PIPs interaction underlies familial vitamin E deficiency2013

    • Author(s)
      Kono N, Ohto U, Hiramatsu T, Urabe M, Uchida Y, Satow Y, Arai H.
    • Journal Title

      Science

      Volume: 340 Issue: 6136 Pages: 1106

    • DOI

      10.1126/science.1233508

    • NAID

      110009807290

    • URL

      https://pure.teikyo.jp/en/publications/56b7af37-eea2-40be-b3c8-ab2816dab44c

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Serum Amyroid A3 binds MD-2 to activates p38 and NF-kB pathway in a MyD88-dependent manner2013

    • Author(s)
      Deguchi A, Tomita T, Omori T, Komatsu A, Ohto U, Takahashi S, Tanimura N, Akashi-Takamura S, Miyake K, Maru Y
    • Journal Title

      J Immunol

      Volume: 191(4) Issue: 4 Pages: 1856-1864

    • DOI

      10.4049/jimmunol.1201996

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] Toll様受容体8(TLR8)と一本鎖RNA複合体の結晶構造2015

    • Author(s)
      丹治裕美、大戸梅治、柴田琢磨、田岡万悟、山内芳雄、礒邊俊明、三宅健介、清水敏之
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸
    • Year and Date
      2015-03-25 – 2015-03-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] 自然免疫受容体NOD2の結晶構造解析2015

    • Author(s)
      前川早貴子、大戸梅治、清水敏之
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸
    • Year and Date
      2015-03-25 – 2015-03-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] Structural study of Toll-like receptor 8 recognizing viral single stranded RNA2014

    • Author(s)
      Umeharu Ohto
    • Organizer
      The International Symposium ‘Molecular basis of host cell competency in virus infection’ 2014
    • Place of Presentation
      Yokohama
    • Year and Date
      2014-11-08 – 2014-11-09
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 自然免疫系Toll様受容体の構造生物学研究2014

    • Author(s)
      大戸梅治、清水敏之
    • Organizer
      第87回日本生化学会年会
    • Place of Presentation
      京都
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] Structural studies of nucleic acid sensing Toll-like receptor2014

    • Author(s)
      U. Ohto, H. Tanji, T. Shibata, K. Miyake, and T. Shimizu
    • Organizer
      23rd Congress and General Assembly of The International Union of Crystallography (IUCr 2014)
    • Place of Presentation
      Montreal, Canada
    • Year and Date
      2014-08-05 – 2014-08-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] TLR8と一本鎖RNAとの複合体の結晶構造2014

    • Author(s)
      丹治裕美、大戸梅治、柴田琢磨、三宅健介、清水敏之
    • Organizer
      第14回日本蛋白質科学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2014-06-25 – 2014-06-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] Crystal structures of human Toll-like receptor 82013

    • Author(s)
      U. Ohto, H. Tanji, T. Shibata, K. Miyake, and T. Shimizu
    • Organizer
      4th International Symposium on Diffraction Structural Biology 2013
    • Place of Presentation
      Nagoya
    • Related Report
      2013 Annual Research Report
  • [Presentation] Structural basis for species-specific endotoxin recognition by TLR4/MD-22013

    • Author(s)
      U. Ohto, K. Fukase, K. Miyake, and T. Shimizu
    • Organizer
      ICSG2013-SLS
    • Place of Presentation
      Sapporo
    • Related Report
      2013 Annual Research Report

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

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