• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2004 Fiscal Year Final Research Report Summary

Structural Biology of Phagocyte oxidation

Research Project

Project/Area Number 14208076
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Structural biochemistry
Research InstitutionHokkaido University

Principal Investigator

INAGAKI Fuyuhiko  Hokkaido University, Grad.School of Pharm.Sci., Professor, 大学院・薬学研究科, 教授 (70011757)

Co-Investigator(Kenkyū-buntansha) OGURA Kenji  Hokkaido University, Grad.School of Pharm.Sci., Instructor, 大学院・薬学研究科, 助手 (50270682)
HORIUCHI Masataka  Hokkaido University, Grad.School of Pharm.Sci., Instructor, 大学院・薬学研究科, 助手 (90322825)
Project Period (FY) 2002 – 2004
Keywordsphagocyte oxidation system / protein-protein interaction / SH3 domain / activation mechanism / auto inhibition / p47 tandem SH3 domains / PRR peptide
Research Abstract

The phagocyte NADPH oxidase, a defense system for microbial infection comprises membrane bound flavocytochrome cyt b_<558> (gp91^<phox> and p22^<phox>) and cytosolic factors including p67^<phox>, p47^<phox>, p40^<phox> and small GTPase Rac. Upon microbial invasion, the cytosolic factors are translocated to the membrane to bind to cyt b_<558>, which activates a redox-core of cyt b_<558> and generates O_2-, a precursor of microbicidal oxidants. The activation of the NADPH oxidase is tightly regulated through conformation change of the tandem SH3 domain of p47^<phox>.
Recently, the crystal structure of the tandem SH3 domains in the autoinhibited form (Groemping et al., Cell,2003, Yuzawa et al., Genes Cells,2004, J Biol Chem.,2004) and the activated form (Groemping et al., Cell,2003) were determined. Interestingly, the tandem SH3 domains formed an intertwisted dimer in the crystal state but the splitted half was considered to be physiologically relevent. Here, we report the three dimensional structures of the masked and unmasked states of the tandem SH3 domains by NMR. Furthermore, we elucidated the global conformation change of the tandem SH3 domains from the masked to unmasked states by small angle X-ray scattering. Based on the present structural data, we discussed the activation mechanism of the phagocyte NADPH oxidase.

  • Research Products

    (43 results)

All 2005 2004 2003 2002 Other

All Journal Article (41 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Structure of a cell polarity regulator, a complex between atypical PKC and Par6 PB1 domains.2005

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

      J.Biol.Chem. 280(10)

      Pages: 9653-9661

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Structure of a cell polarity regulator, a complex between atypical PKC and Par6 PB1 domains.2005

    • Author(s)
      Hirano, Y
    • Journal Title

      J.Biol.Chem. 280(10)

      Pages: 9653-9661

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Sequence-specific resonance assignments of the tandem SH3 domains in an autoinhibitory form of p47^<phox>.2004

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

      J.Biomol.NMR 29

      Pages: 451-452

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Structural basis for the specificity, catalysis, and regulation of human uridine-cytidine kinase.2004

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

      Structure 12

      Pages: 751-764

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A molecular mechanism for autoinhibition of the tandem SH3 domains of p47^<phox>, the regulatory subunit of the phagocyte NADPH oxidase.2004

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

      Genes Cells 9

      Pages: 443-456

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Solution structure of the tandem SH3 domains of p47^<phox> in an autoinhibited form.2004

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

      J.Biol.Chem. 279

      Pages: 29752-29760

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Binding of FAD to cytochrome b558 is facilitated during activation of the phagocyte NADPH oxidase, leading to superoxide production.2004

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

      J.Biol.Chem. 279(25)

      Pages: 26378-26386

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The Crystal Structure of Microtuble-Associated Protein Light Chain 3, a Mammalian Homologue of Saccharomyces cerevisiae Atg8.2004

    • Author(s)
      Sugawara, K.
    • Journal Title

      Genes Cells. 9

      Pages: 611-618

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Solution structure of atypical PKC PB1 domain and its mode of interaction with ZIP/p62 and MEK5.2004

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

      J.Biol.Chem. 279(30)

      Pages: 31883-31890

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 細胞極性化に関与するPB1ドメインの構造生物学-ユビキチンフォールドに秘められた巧妙な戦略-2004

    • Author(s)
      吉永壮佐
    • Journal Title

      細胞工学 23,4

      Pages: 468-472

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] SH3ドメインの分子認識機構 Structural basis of target recognition by SH3 domain2004

    • Author(s)
      湯沢聡
    • Journal Title

      生体の化学 55

      Pages: 164-170

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Sequence-specific resonance assignments of the tandem SH3 domains in an autoinhibitory form of of p47^<phox>.2004

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

      J.Biomol.NMR 29

      Pages: 451-452

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Structural basis for the specificity, catalysis, regulation of human uridine-cytidine kinase.2004

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

      Structure 12

      Pages: 751-764

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A molecular mechanism for for autoinhibition of the tandem SH3 domains of p47^<phox.>, the regulatory subunit of the phagocyte NADPH oxidase.2004

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

      Genes Cells. 9

      Pages: 443-456

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Solution structure of atypical PKC PB1 domain and its mode of interaction with ZIP/p62 and MEK5.2004

    • Author(s)
      Hirano, Y
    • Journal Title

      J.Biol.Chem. 279(30)

      Pages: 1883-1890

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Crystallization and preliminary crystallographic analysis of DJ-1, a protein associated with male fertility and parkinsonism.2003

    • Author(s)
      Honbou, K.
    • Journal Title

      Acta Crystallogr D Biol Crystallogr. 59(Pt 8)

      Pages: 1502-1503

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Backbone assignments of Grb2 complexed with ligand peptides for SH3 and SH2 domains.2003

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

      J Biomol NMR 27

      Pages: 185-186

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Crystallization and preliminary crystallographic analysis of the autoinhibited form of the tandem SH3 domain of p47(phox).2003

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

      Acta Crystallogr.D Biol.Crystallogr.

      Pages: 1479-1480

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Crystallization and preliminary X-ray analysis of human uridine-cytidine kinase 22003

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

      Acta Crystallogr.D Biol.Crystallogr. 59

      Pages: 1477-1478

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The PB1 domain and the PC motif-containing region are structurally similar protein binding modules.2003

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

      EMBO J. 22

      Pages: 4888-4897

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The crystal structure of DJ-1, a protein related to male fertility and Parkinson's disease.2003

    • Author(s)
      Honbou, K.
    • Journal Title

      J.Biol.Chem. 278

      Pages: 31380-31384

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] X-ray crystal structure of IRF-3 and its functional implications.2003

    • Author(s)
      Takahasi, K.
    • Journal Title

      Nat.Struct.Biol. 10

      Pages: 922-927

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Crystallization and preliminary X-ray analysis of LC3-I.2003

    • Author(s)
      Sugawara, K.
    • Journal Title

      Acta Crystallogr.D Biol.Crystallogr. 59

      Pages: 1464-1465

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Identification of Ser 386 of interferon regulatory factor 3 as critical targets for inducible phosphorylation that determines activation.2003

    • Author(s)
      Mori, M.
    • Journal Title

      J.Biol.Chem. 279

      Pages: 9698-9702

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Molecular Recognition in Dimerization between PB1 Domains.2003

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

      J.Biol.Chem. 278

      Pages: 43516-43524

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] SH3相互の新規認識2003

    • Author(s)
      稲垣冬彦
    • Journal Title

      Medical Science Digest 29,2

      Pages: 30-33

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Backbone assignments of Grb2 complexed with ligand peptides for SH3 and SH2 domains2003

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

      J Biomol NMR 27

      Pages: 185-186

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Crystallization and preliminary crysrtallographic analysis of the autoinhibited form of the tandem SH3 domain of p47(phox).2003

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

      Acta Crystallogr.D Biol.Crystallogr.

      Pages: 1479-1480

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Crystallization and preliminary X-ray analysis of human uridine-cytidine kinase 2.2003

    • Author(s)
      Suzuki, N
    • Journal Title

      Acta Crystallogr.D Biol.Crystallogr. 59

      Pages: 1477-1478

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The PB1 domain and the PC motif-containing region are structurally similar protein binding modules.2003

    • Author(s)
      Yoshinaga
    • Journal Title

      EMBO J 22

      Pages: 4888-4897

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The crystal structure of DJ-1, a protein related to male fertility and Parkinson's disease.2003

    • Author(s)
      Honbou, K
    • Journal Title

      J.Biol.Chem. 278

      Pages: 31380-31384

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Crystallization and preliminary X-ray analysis of LC3-I.2003

    • Author(s)
      Sugawara, K
    • Journal Title

      Acta Crystallogr.D Biol.Crystallogr. 59

      Pages: 1464-1465

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Identification of Ser 386 of interferon regulatory factor3 as critical targets for inducile phosphorylation that determines activation.2003

    • Author(s)
      Mori, M.
    • Journal Title

      J.Biol.Chem. 279

      Pages: 9698-9702

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Molecular Recognition in Dimerization between PB1 Domains.2003

    • Author(s)
      Noda, Y
    • Journal Title

      J.Biol.Chem. 278

      Pages: 43516-43524

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Solution structure of N-terminal SH3 domain of Vav and the recognition site for Grb2 C-terminal SH3 domain.2002

    • Author(s)
      Ogura, K.
    • Journal Title

      J.Biomol.NMR 22

      Pages: 37-46

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] OPR, PC and AID : all in the PB1 family.2002

    • Author(s)
      Ponting, C.P.
    • Journal Title

      TIBS 27

      Pages: 10

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Grb2を介するシグナル伝達の構造生物学2002

    • Author(s)
      稲垣冬彦
    • Journal Title

      生化学 74

      Pages: 1229-1236

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 新規ドメインPB1の構造と機能-シグナル伝達における役割-2002

    • Author(s)
      吉永壮佐
    • Journal Title

      蛋白質 核酸 酵素 47,8

      Pages: 941-947

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Solution structure of N-terminal SH3 domain of Vav and the recognition site for Grb2 C-terminal SH3 domain.2002

    • Author(s)
      Ogura, K
    • Journal Title

      J.Biomol.NMR 22

      Pages: 37-46

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Crystallization and preliminary crystallographic analysis of DJ-1, a protein associated with male fertility and parkinsonism.

    • Author(s)
      Honbou, K.
    • Journal Title

      Acta Crystallogr D Biol Crystallogr.2003 Aug, 59(Pt8)

      Pages: 1502-1503

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Binding of FAD to cytochrome b558 is facilitated during activation of the phagocyte NADPH oxidase, leading to superoxide production.

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

      J.Biol.Chem. 279(25)

      Pages: 26378-36386

    • Description
      「研究成果報告書概要(欧文)」より
  • [Patent(Industrial Property Rights)] シグナル伝達活性を有する細胞質蛋白質の活性制御方法2003

    • Inventor(s)
      稲垣 冬彦, 橋田 修吉
    • Industrial Property Rights Holder
      北海道大学
    • Industrial Property Number
      特願2003-409281(2003)
    • Filing Date
      2003-12-08
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] NADPHオキシダーゼ活性を阻害するポリペプチド2003

    • Inventor(s)
      稲垣 冬彦, 橋田 修吉
    • Industrial Property Rights Holder
      北海道大学
    • Industrial Property Number
      特願2003-409282(2003)
    • Filing Date
      2003-12-08
    • Description
      「研究成果報告書概要(和文)」より

URL: 

Published: 2006-07-11  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi