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Structural Biology of Innate Immunity

Research Project

Project/Area Number 17109002
Research Category

Grant-in-Aid for Scientific Research (S)

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionHokkaido University

Principal Investigator

INAGAKI Fuyuhiko  Hokkaido University, 大学院・薬学研究院, 教授 (70011757)

Co-Investigator(Kenkyū-buntansha) NODA Nobuo  北海道大学, 大学院・薬学研究院, 講師 (40396297)
OGURA Kenji  北海道大学, 大学院・薬学研究院, 助教 (50270682)
HORIUCHI Masataka  北海道大学, 大学院・薬学研究院, 助教 (90322825)
Project Period (FY) 2005 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥114,270,000 (Direct Cost: ¥87,900,000、Indirect Cost: ¥26,370,000)
Fiscal Year 2009: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2008: ¥27,690,000 (Direct Cost: ¥21,300,000、Indirect Cost: ¥6,390,000)
Fiscal Year 2007: ¥27,690,000 (Direct Cost: ¥21,300,000、Indirect Cost: ¥6,390,000)
Fiscal Year 2006: ¥22,100,000 (Direct Cost: ¥17,000,000、Indirect Cost: ¥5,100,000)
Fiscal Year 2005: ¥31,200,000 (Direct Cost: ¥24,000,000、Indirect Cost: ¥7,200,000)
Keywords自然免疫 / 好中球活性酸素発生系 / NADPH酸化酵素 / SH3ドメイン / PXドメイン / インターフェロン産生系 / TLR / TIR / IRF-3 / リン酸化 / Βgrp / β1-3グルカン / インターフェロン / 活性制御 / RLR / βGRP / TIRドメイン / TICAM1 / TRIF / TRAM / 細胞質因子 / p40 / ファゴソーム / PI(3)P / RIGI / CARDドメイン
Research Abstract

(1)We elucidated the molecular mechanism for tethering p^<47> and p^<40> to cyt b558 or membrane on the structural basis.
(2)We found that IRF-3 is phosphorylated by IKKi at Ser386 and form a homodimer to bind CBP/p300in vitro and produces type Iinterferons.
(3)RIG-I like receptor family proteins (RLR) play essential roles to recognize double stranded RNA (dsRNA) in cytosol. We found that the C terminal domain of RLR recognizes viral specific dsRNA. Wedetermined the structure of C-terminal domain of RLR and discussed the specific interaction with viral specific dsRNA.
(4)dsRNA and LPS bind to TLR3 and TLR4, respectively to activate downstream signaling to producetype 1 interferons. Here, we determined the structure of TIR domains of TRIF and TRAM andelucidated their oligomerization process which is essential for down stream signaling.
(5)We elucidated the recognition mechanism of β1-3 glucan by βGRP from Bombyx Mori.

Report

(6 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • Research Products

    (61 results)

All 2009 2008 2007 2006 2005 Other

All Journal Article (45 results) (of which Peer Reviewed: 27 results) Presentation (15 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Solution structure of the silkworm βGRP/GNBP3 N-terminal domain reveals the mechanism for β-1, 3-glucan-specific recognition.2009

    • Author(s)
      Takahasi K., Ochiai M., Horiuchi M., Kumeta H., Ogura K., Ashida M., Inagaki F.
    • Journal Title

      Proc Natl Acad Sci U S A 106

      Pages: 11679-11684

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] The Domain Organization of p67phox, a Protein Required for Activation of the Superoxide-Producing NADPH Oxidase in Phagocytes.2009

    • Author(s)
      Yuzawa S., Miyano K., Honbou K., Inagaki F., Sumimoto H.
    • Journal Title

      J Innate Immun. 1

      Pages: 543-555

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Solution structures of cytosolic RNA sensor MDA5 and LGP2 C-lerminal domains : identification of the RNA recognition loop in RIG-I-like receptors.2009

    • Author(s)
      Takahasi K
    • Journal Title

      J Biol Chem 284

      Pages: 17465-17474

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Solution structure of the silkworm{beta}GRP/GNBP3 N-terminal domain reveals the mechanism for{beta}-1,3-glucan-specific recognition.2009

    • Author(s)
      Takahasi K
    • Journal Title

      Proc Natl Acad Sci USA 106

      Pages: 11679-11684

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ATG systems from the protein structural point of view.2009

    • Author(s)
      Noda NN
    • Journal Title

      Chemical Review 109

      Pages: 1587-1598

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Atg systems from the protein structural point of view2009

    • Author(s)
      Noda N
    • Journal Title

      Chemical Reviews (in printing)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nonself RNA-Sensing Mechanism of RIG-I Helicase and Activation of Antiviral Immune Responses.2008

    • Author(s)
      Takahasi K., Yoneyama M., Nishihori T., Hirai R., Kumeta H., Narita R., Gale M. Jr, Inagaki F, Fujita T.
    • Journal Title

      Mol. Cell 29

      Pages: 428-440

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Structural basis of target recognition by Atg8 / LC3 during selective autophagy2008

    • Author(s)
      Noda N
    • Journal Title

      Genes Cell 13

      Pages: 1211-1218

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Solution structure of the Grb2 SH2 domain complexed with a high-affinity inhibitor2008

    • Author(s)
      Ogura K
    • Journal Title

      J Biomol. NMR 42

      Pages: 197-207

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The NMR structure of the NIPP1 FHA domain2008

    • Author(s)
      Kumeta H
    • Journal Title

      J. Biomol., NMR 40

      Pages: 219-224

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nonself RNA-Sensing Mechanism of RIG-I Helicase and Activation of Antiviral Immune Responses2008

    • Author(s)
      Takahasi K
    • Journal Title

      Mol. Cell 29

      Pages: 428-440

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] p40^<phox>の結晶構造と活性酸素発生の制御機構2008

    • Author(s)
      本坊和也
    • Journal Title

      生化学 80

      Pages: 743-747

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 細胞内シグナル伝達2008

    • Author(s)
      稲垣冬彦
    • Journal Title

      蛋白質核酸酵素 53

      Pages: 600-603

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The NMR structure of the NIPP1 FHA domain.2008

    • Author(s)
      Kumeta H
    • Journal Title

      J. Biomol. NMR. (in press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nonself RNA-Sensing Mechanism of RIG-I Helicase and Activation of Antiviral Immune Responses.2008

    • Author(s)
      Takahasi K
    • Journal Title

      Mol. Cell. 29

      Pages: 428-440

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In vitro reconstitution of plant ATG8 and ATG12 conjugation systems essential for autophagy.2008

    • Author(s)
      Fujioka Y
    • Journal Title

      J. Biol. Chem. 283

      Pages: 1921-1928

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 構造が解き明かすアダプター蛋白質Crkの癌化機構、「蛋白質核酸酵素2008

    • Author(s)
      小橋川敬博
    • Journal Title

      蛋白質核酸酵素 53

      Pages: 148-156

    • Related Report
      2007 Annual Research Report
  • [Journal Article] 構造が解き明かすアダプターCRKのシグナル伝達2008

    • Author(s)
      小橋川敬博
    • Journal Title

      実験医学 25

      Pages: 2887-2890

    • Related Report
      2007 Annual Research Report
  • [Journal Article] 極性発現に必要なPB1ドメイン間の相互作用2008

    • Author(s)
      稲垣冬彦
    • Journal Title

      生体の科学 58

      Pages: 402-403

    • Related Report
      2007 Annual Research Report
  • [Journal Article] Full-length p40phox structure suggests a basis for regulation mechanism of its membrane binding.2007

    • Author(s)
      Honbou K., Minakami R., Yuzawa S., Takeya R., Suzuki N.N., Kamakura S., Sumimoto H., Inagaki F.
    • Journal Title

      EMBO J 26

      Pages: 1176-1186

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Crystallization and preliminary crystallographic analysis of Tob-hCafl complex.2007

    • Author(s)
      Nishida K
    • Journal Title

      Acta Crystallograph. Sect. F Struct. Biol. Cryst. Commun. 63

      Pages: 1061-1063

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Crystallization of the Atg12-Atg5 conjugate bound to Atg16 by the free interface diffusion method2007

    • Author(s)
      Noda N
    • Journal Title

      J. Synchrotron Radiat. (in press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The ATG12-ATG5 conjugate has a novel e3-like activity for protein lipidation in autophagy2007

    • Author(s)
      Hanada T
    • Journal Title

      J. Biol. Chem. 282

      Pages: 37298-37302

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An efficient method for protein phosphorylation using the artificially introduced of cognate-binding modules into kinases and substrates.2007

    • Author(s)
      Kobashigawa Y
    • Journal Title

      J Biotechnol. 131

      Pages: 458-465

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Cooperative Role of OsCnfU-1A Domain I and Domain II in the Iron-Sulfur Cluster Transfer Process as Revealed by NMR.2007

    • Author(s)
      Saio T
    • Journal Title

      J. Biochem.(Tokyo). 142

      Pages: 113-121

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Crystallization and preliminary X-ray analysis of Atg10.2007

    • Author(s)
      Yamaguti M
    • Journal Title

      Acta Crystallograph. Sect. F Struct. Biol. Cryst. Commun. 63

      Pages: 443-445

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The NMR structure of the domain II of a chloroplastic NifU-like protein OsNifU1A.2007

    • Author(s)
      Kumeta H
    • Journal Title

      J. Biomol. NMR 38

      Pages: 161-4

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structural basis for the transforming activity of human cancer-related signaling adaptor protein CRK.2007

    • Author(s)
      Kobashigawa Y
    • Journal Title

      Nat. Struct. Mol. Biol. 14

      Pages: 503-510

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Grb2 SH2の構造を基盤とした抗ガン剤の設計2007

    • Author(s)
      稲垣冬彦
    • Journal Title

      医薬ジャーナル 43

      Pages: 5-10

    • Related Report
      2007 Annual Research Report
  • [Journal Article] オートファジーの構造生物学2007

    • Author(s)
      鈴木展生
    • Journal Title

      生物物理 47

      Pages: 107-111

    • NAID

      10031202188

    • Related Report
      2007 Annual Research Report
  • [Journal Article] The crystal structure of ATG3, an autophagy-related E2 enzyme that mediates ATG8 lipidation.2007

    • Author(s)
      Yamada Y.
    • Journal Title

      J. Biol. Chem. (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Full-length p40phox structure suggests a basis for regulation mechanism of its membrane binding.2007

    • Author(s)
      Honbou K.
    • Journal Title

      EMBO J. 26(4)

      Pages: 1176-1786

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Structure of Atg5・Atg16, a complex essential for autophagy.2007

    • Author(s)
      Matsushita M.
    • Journal Title

      J. Biol. Chem. 282(9)

      Pages: 6763-6732

    • Related Report
      2006 Annual Research Report
  • [Journal Article] NMR Solution Structure of the Tandem Src Homology 3 Domains p47phox Complexed with a p22phox-derived Proline-rich Peptide.2006

    • Author(s)
      Ogura K., Nobuhisa I., Yuzawa S., Takeya R., Torikai S., Saikawa K., Sumimoto H., Inagaki F.
    • Journal Title

      J. Biol. Chem 281

      Pages: 3660-3668

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Activation of the superoxide-producing phagocyte NADPH oxidase requires co-operation between the tandem SH3 domains of p47phox in recognition of a polyproline type II helix and an adjacent alpha-helix of p22phox.2006

    • Author(s)
      Nobuhisa I., Takeya R., Ogura K., Ueno N., Kohda D., Inagaki F. Sumimoto H.
    • Journal Title

      Biochem. J 396

      Pages: 183-192

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Crystallization and preliminary crystallographic analysis of p40phox, a regulatory subunit of NADPH oxidase.2006

    • Author(s)
      Honbou K.
    • Journal Title

      Acta Crystallograph Sect F Struct Biol Cryst Commun. 62(Pt 10)

      Pages: 1018-1020

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Activation of the superoxide-producing phagocyte NADPH oxidase requires co-operation between the tandem SH3 domains of p47phox in recognition of a polyproline type II helix and an adjacent alpha-helix of p22phox.2006

    • Author(s)
      Nobuhisa I.
    • Journal Title

      Biochem. J. 396(l)

      Pages: 183-192

    • Related Report
      2006 Annual Research Report
  • [Journal Article] NMR Solution Structure of the Tandem Src Homology 3 Domains of p47phox Complexed with a p22phox-derived Proline-rich Peptide.2006

    • Author(s)
      Ogura K.
    • Journal Title

      J Biol Chem. 281(6)

      Pages: 3660-3668

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 1H, 13C and 15N resonance assignments of the backbone and methyl groups of the 24 kDa tetratricopeptide repeat domain in p67(phox).2005

    • Author(s)
      Yoshida, S.
    • Journal Title

      J.Biomol.NMR. 32(2)

      Pages: 176-176

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Refolding and purification of recombinant OsNifU1A domain II that was expressed by Escherichia coli.2005

    • Author(s)
      Katoh, S.
    • Journal Title

      Protein Expr Purif. 43(2)

      Pages: 149-156

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Structural basis for the specificity and catalysis of human Atg4B responsible for mammalian autophagy.2005

    • Author(s)
      Sugawara K.
    • Journal Title

      J Biol Chem. 280(48)

      Pages: 40058-40065

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Conformational change in full-length mouse prion : A site-directed spin-labeling study.2005

    • Author(s)
      Inanami, O.
    • Journal Title

      Biochem Biophys Res Commun. 335(3)

      Pages: 785-792

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The crystal structure of plant ATG12 and its biological implication in autophagy.2005

    • Author(s)
      Suzuki, N. N.
    • Journal Title

      Autophagy 1

      Pages: 119-126

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Tor2 directly phosphorylates the AGC kinase Ypk2 to regulate actin polarization.2005

    • Author(s)
      Kamada, Y.
    • Journal Title

      Mol Cell Biol. 25(16)

      Pages: 7239-7248

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Solution structures of cytosolic RNA sensor MDA5 and LGP2 C-terminal domains: identification of the RNA recognition loop in RIG-I-like receptors.

    • Author(s)
      Takahasi K., Kumeta H., Tsuduki N., Narita R., Shigemoto T., Hirai R., Yoneyama M., Horiuchi M., Ogura K., Fujita T., Inagaki F.
    • Journal Title

      J Biol Chem

      Pages: 17465-17474

    • NAID

      120001415118

    • Related Report
      2009 Final Research Report
  • [Presentation] RIG-I-like receptorの生化学的、構造学的機能解析2009

    • Author(s)
      成田亮
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Year and Date
      2009-12-09
    • Related Report
      2009 Annual Research Report
  • [Presentation] TICAM-1およびTICAM-2 TIRドメインの溶液構造2009

    • Author(s)
      久米田博之
    • Organizer
      第48回NMR討論会
    • Place of Presentation
      九州大学馬出病院キャンパス医学部百年講堂
    • Related Report
      2009 Final Research Report
  • [Presentation] Soft interaction in phagocyte oxidation system2009

    • Author(s)
      稲垣冬彦
    • Organizer
      International Symposium on Molecular Soft Interactions in Biological Systems
    • Place of Presentation
      千里ライフサイエンスセンター
    • Related Report
      2009 Final Research Report
  • [Presentation] NMR構造生物学の新展開2008

    • Author(s)
      稲垣冬彦
    • Organizer
      平成20年度日本分光学会NMR分光部会シンポジウム
    • Place of Presentation
      東京大学薬学部講堂
    • Year and Date
      2008-09-01
    • Related Report
      2008 Annual Research Report
  • [Presentation] 常磁性ランタニドプローブ法のタンパク室構造解析への応用2008

    • Author(s)
      稲垣冬彦
    • Organizer
      BMB2008
    • Place of Presentation
      神戸ポートアイランド
    • Related Report
      2008 Annual Research Report
  • [Presentation] Solution structure of RIG-like receptor C-terminal domains2008

    • Author(s)
      Fuyuhiko Inagaki
    • Organizer
      回日本免疫学会総会・学術集会・国際シンポジウム
    • Place of Presentation
      国立京都国際会館
    • Related Report
      2008 Annual Research Report
  • [Presentation] Structural Biology of Autophagy. International Conference On Structural Genomics Organization2008

    • Author(s)
      Fuyuhiko Inagaki
    • Organizer
      International Conference On Structural Genomics Organization
    • Place of Presentation
      University of Oxford
    • Related Report
      2008 Annual Research Report
  • [Presentation] Structural basis for the transforming activity of human-cancer related s ignaling adaptor protein CRK2008

    • Author(s)
      Fuyuhiko Inagaki
    • Organizer
      International Conference Magnetic in Biological Systems
    • Place of Presentation
      San Diego
    • Related Report
      2008 Annual Research Report
  • [Presentation] Structural Basis for the Transforming Activity of Human Cancer-related Signaling Adaptor Protein Crk.2008

    • Author(s)
      Yoshihiro Kobashigawa
    • Organizer
      Korean NMR Society Meeting
    • Place of Presentation
      Seoul, Korea. Yonsei University
    • Related Report
      2007 Annual Research Report
  • [Presentation] Structural biology of autophagy2008

    • Author(s)
      Fuyuhiko Inagaki
    • Organizer
      The 9th RIES-Hokudai International Symposium
    • Place of Presentation
      Sapporo創造的研究イニシアティブ"sousei"
    • Related Report
      2007 Annual Research Report
  • [Presentation] Structural basis for the transforming activity of human cancer-related signaling adaptor protein CRK2007

    • Author(s)
      Fuyuhiko Inagaki
    • Organizer
      よこはまNMR構造生物学研究会「International Symposium on Drug Discovery and Design by NMR」
    • Place of Presentation
      横浜 理化学研究所横浜研究所 交流棟ホール
    • Year and Date
      2007-10-22
    • Related Report
      2007 Annual Research Report
  • [Presentation] Structural Basis for the regulation of Phagocyte NADPH Oxidase Activity2007

    • Author(s)
      Fuyuhiko Inagaki
    • Organizer
      The 16th ISMAR conference
    • Place of Presentation
      Kenting, Taiwan
    • Related Report
      2009 Final Research Report
  • [Presentation] Structural Basis for the regulation of Phagocyte NADPH Oxidase Activity. The 16th ISMAR conference2007

    • Author(s)
      Fuyuhiko Inagaki
    • Organizer
      The 16th ISMAR conference,
    • Place of Presentation
      Taiwan Howard Beach Resort Kenting
    • Related Report
      2007 Annual Research Report
  • [Presentation] Structural basis for superoxide generation by phagocyte NADPH oxidase2007

    • Author(s)
      Fuyuhiko Inagaki
    • Organizer
      The 2nd Asia-Pacific NMR Symposium
    • Place of Presentation
      Hsinchu, Taiwan. Lakeshore Hotel
    • Related Report
      2007 Annual Research Report
  • [Presentation] Structural analysis of human cancer related adaptor protein Crk and its biological implications.2007

    • Author(s)
      Fuyuhiko Inagaki
    • Organizer
      The KIAS-Soongsil Conference on Protein Structure and Function(7th Conference)
    • Place of Presentation
      Seoul, Korea. Soongsil University
    • Related Report
      2007 Annual Research Report
  • [Patent(Industrial Property Rights)] リン酸化タンパク質の製法2006

    • Inventor(s)
      小橋川敬博, 内藤雅人, 稲垣冬彦
    • Industrial Property Rights Holder
      北海道大学
    • Industrial Property Number
      2005-359966
    • Filing Date
      2006-02-21
    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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