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Structural and functional basis of the complex of mono-ADP-ribosylating toxin and substrate protein

Research Project

Project/Area Number 21570121
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Structural biochemistry
Research InstitutionKyoto Sangyo University (2010-2011)
Tokushima Bunri University (2009)

Principal Investigator

TSUGE Hideaki  京都産業大学, 総合生命科学部, 教授 (40299342)

Co-Investigator(Renkei-kenkyūsha) SAKURAI Jun  徳島文理大学, 薬学部, 教授 (80029800)
NAGAHAMA Masahiro  徳島文理大学, 薬学部, 教授 (40164462)
ODA Masataka  徳島文理大学, 薬学部, 講師 (00412403)
Research Collaborator TSURUMURA Toshiharu  京都産業大学, 総合生命科学部, プロジェクト助教 (50450250)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsC3 / RhoA / Ia / アクチン / モノADPリボシル化 / 結晶構造解析 / 特異性 / 複合体結晶構造解析 / ADPリボシルトランスフェラーゼ / 細菌毒素 / X線結晶構造解析 / 複合体解析 / C3毒素
Research Abstract

To reveal the structural and functional mechanism of C. perfringens iota toxin(Ia) and actin, we successfully crystallized and solved the structure of the apo-Ia-actin and apo-Ia. We revealed the structural change upon the ADP-ribosylation by comparing the structures together with NADH-Ia and βTAD-Ia-actin complex.
C. Botulinum C3 toxin ADP-ribosylates RhoA Asn41. For the structure analysis of C3-RhoA complex, RhoA was expressed in E. coli and the stable mutant of RhoAF25N was obtained using His-tag and GST-tag, independently. We are currently searching the crystallization condition for the complex.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report

Research Products

(45 results)

All 2012 2011 2010 2009 Other

All Journal Article (21 results) (of which Peer Reviewed: 21 results) Presentation (20 results) Remarks (4 results)

  • [Journal Article] Structural basis of the free reduced flavin generation by flavin reductase from Thermus thermophilus HB82011

    • Author(s)
      Imagawa T, Tsurumura T, Sugimoto Y, Aki K, Ishidoh K, Kuramitsu S, Tsuge H
    • Journal Title

      J Biol Chem

      Volume: 286(51) Pages: 44078-85

    • URL

      http://www.ncbi.nlm.nih.gov/pubmed/22052907

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Structure and stability of Gyuba, β-lactoglobulin chimera2011

    • Author(s)
      Ohtomo H, Konuma T, Utsunomiya H, Tsuge H, Ikeguchi M
    • Journal Title

      Protein Sci.

      Volume: 20(11) Pages: 1867-1875

    • DOI

      10.1002/pro.720

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] The catalytic mechanism of dye-decolorizing peroxidase DyP may require the swinging movement of an aspartic acid residue2011

    • Author(s)
      Yoshida T, Tsuge H, Konno H, Hisabori T, Sugano Y
    • Journal Title

      FEBS J

      Volume: 278(13) Pages: 2387-94

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] The catalytic mechanism of dye-decolorizing peroxidase DyP may require the swinging movement of an aspartic acid residue2011

    • Author(s)
      Yoshida T, Tsuge H, Konno H, Hisabori T, Sugano Y
    • Journal Title

      FEBS.J

      Volume: 278 Pages: 2387-2394

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structural basis of free reduced flavin generation by flavin reductase from Thermus thermophilus HB82011

    • Author(s)
      Imagawa T, Tsurumura T, Sugimoto Y, Aki K, Ishidoh K, Kuramitsu S, Tsuge H
    • Journal Title

      J Biol Chem.

      Volume: 286(51) Pages: 44078-44085

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nucleolin as cell surface receptor for tumor necrosis factor-alpha inducing protein : a carcinogenic factor of Helicobacter pylori2010

    • Author(s)
      Watanabe T, Tsuge H, Imagawa T, Kise D, Hirano K, Beppu M, Takahashi A, Yamaguchi K, Fujiki H, Suganuma M
    • Journal Title

      J Cancer Res Clin Oncol

      Volume: 136(6) Pages: 911-21

    • URL

      http://www.ncbi.nlm.nih.gov/pubmed/20049476

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Nucleolin as cell surface receptor for tumor necrosis factor-alpha inducing protein : a carcinogenic factor of Helicobacter pylori.2010

    • Author(s)
      Watanabe T, Tsuge H, Imagawa T, Kise D, Hirano K, Beppu M, Takahashi A, Yamaguchi K, Fujiki H, Suganuma M.
    • Journal Title

      J Cancer Res Clin Oncol.

      Volume: 136(6) Pages: 911-21

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nucleolin as cell surface receptor for tumor necrosis factor-alpha inducing protein : a carcinogenic factor of Helicobacter pylori2010

    • Author(s)
      Watanabe T., Tsuge H., 等
    • Journal Title

      J Cancer Res Clin Oncol. (In press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The carboxy-terminal tail of Aeromonas sobria Serine Protease is associated with the chaperone2009

    • Author(s)
      Kobayashi H, Tateishi A, Tsuge H, Takahashi E, Okamoto K, Yamanaka H
    • Journal Title

      Microbiol Immunol

      Volume: 53(12) Pages: 647-57

    • NAID

      10027687949

    • URL

      http://www.ncbi.nlm.nih.gov/pubmed/19954452

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Structural basis for the kexin-like serine protease from Aeromonas sobria as sepsis-causing factor2009

    • Author(s)
      Kobayashi H, Utsunomiya H, Yamanaka H, Sei Y, Katunuma N, Okamoto K, Tsuge H
    • Journal Title

      J Biol Chem

      Volume: 284(40) Pages: 27655-63

    • URL

      http://www.ncbi.nlm.nih.gov/pubmed/19954452

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Structural basis for the Helicobacter pylori-carcinogenic TNF-alpha-inducing protein2009

    • Author(s)
      Tsuge H, Tsurumura T, Utsunomiya H, Kise D, Kuzuhara T, Watanabe T, Fujiki H, Suganuma M
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 388(2) Pages: 193-8

    • URL

      http://www.ncbi.nlm.nih.gov/pubmed/19643085

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Refolding, characterization and crystal structure of(S)-malate dehydrogenase from the hyperthermophilic archaeon Aeropyrum pernix2009

    • Author(s)
      Kawakami R, Sakuraba H, Goda S, Tsuge H, Ohshima T
    • Journal Title

      Biochim Biophys Acta

      Volume: 1794(10) Pages: 1496-504

    • NAID

      120007015445

    • URL

      http://www.ncbi.nlm.nih.gov/pubmed/19555779

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Crystallization and X-ray diffraction analysis of the RNA primer/promoter-binding domain of influenza A virus RNA-dependent RNA polymerase PB22009

    • Author(s)
      Kuzuhara T, Kise D, Yoshida H, Horita T, Murazaki Y, Utsunomiya H, Tsuge H
    • Journal Title

      Acta Crystallogr Sect F Struct Biol Cryst Commun

      Volume: 65 Pages: 144-6

    • URL

      http://www.ncbi.nlm.nih.gov/pubmed/19194006

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Structural basis of the influenza A virus RNA polymerase PB2 RNA-binding domain containing the pathogenicity-determinant lysine 627 residue2009

    • Author(s)
      Kuzuhara T, Kise D, Yoshida H, Horita T, Murazaki Y, Nishimura A, Echigo N, Utsunomiya H, Tsuge H
    • Journal Title

      J Biol Chem

      Volume: 284(11) Pages: 6855-60

    • URL

      http://www.ncbi.nlm.nih.gov/pubmed/19144639

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Non-native alpha-helix formation is not necessary for folding of lipocalin : comparison of burst-phase folding between tear lipocalin and beta-lactoglobulin2009

    • Author(s)
      Tsukamoto S, Yamashita T, Yamada Y, Fujiwara K, Maki K, Kuwajima K, Matsumura Y, Kihara H, Tsuge H, Ikeguchi M
    • Journal Title

      Proteins

      Volume: 76(1) Pages: 226-36

    • URL

      http://www.ncbi.nlm.nih.gov/pubmed/19137619

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Structural analysis of human glutamine : fructose-6-phosphate amidotransferase, a key regulator in type 2 diabetes2009

    • Author(s)
      Nakaishi Y, Bando M, Shimizu H, Watanabe K, Goto F, Tsuge H, Kondo K, Komatsu M
    • Journal Title

      FEBS Lett

      Volume: 583(1) Pages: 163-7

    • URL

      http://www.ncbi.nlm.nih.gov/pubmed/19059404

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Refolding characterization and crystal structure of(S)-malate dehydrogenase from the hyperthermophilic archaeon Aeropyrum pernix2009

    • Author(s)
      Kawakami R., Tsuge H., 等
    • Journal Title

      Biochim Biophys Acta. 1794-10

      Pages: 1496-1504

    • NAID

      120007015445

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structural basis for the Helicobacter pylori-carcinogenic TNF-alpha-inducing protein2009

    • Author(s)
      Tsuge H., Tsurumura T., 等
    • Journal Title

      Biochem Biophys Res Commun. 388-2

      Pages: 193-198

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structural basis for the kexin-like serine protease from Aeromonas sobria as a sepsiscausing factor2009

    • Author(s)
      Kobayashi H., Tsuge H., 等
    • Journal Title

      J Biol Chem. 284-40

      Pages: 27655-27663

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The carboxy-terminal tail of Aeromonas sobria serine protease is associated with the chaperone2009

    • Author(s)
      Kobayashi H., Tsuge H., 等
    • Journal Title

      Microbiol Immunol. 53-12

      Pages: 647-657

    • NAID

      10027687949

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clostridium perfringens Iota-Toxin : Structure and Function2009

    • Author(s)
      Sakurai J., Tsuge H., 等
    • Journal Title

      Toxins. 1

      Pages: 208-228

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] ADPリボシル化反応に伴う酵素の構造変化2012

    • Author(s)
      津下英明
    • Organizer
      ビタミンB研究協議会
    • Place of Presentation
      京都国際交流会館
    • Year and Date
      2012-02-04
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] ADPリボシル化毒素構造研究の最前線2011

    • Author(s)
      津下英明
    • Organizer
      シンポジウム「疾患治療に用いる天然有機化合物の生合成遺伝子の包括的理解」
    • Place of Presentation
      徳島文理大学
    • Year and Date
      2011-12-22
    • Related Report
      2011 Final Research Report
  • [Presentation] ADPリボシル化毒素構造研究の最前線2011

    • Author(s)
      津下英明
    • Organizer
      シンポジウム「疾患治療に用いる天然有機化合物の生合成遺伝子の包括的理解」
    • Place of Presentation
      徳島文理大学(招待講演)
    • Year and Date
      2011-12-22
    • Related Report
      2011 Annual Research Report
  • [Presentation] アクチンADPリボシル化の構造基盤2011

    • Author(s)
      津下英明
    • Organizer
      シンポジウム「ADPリボシル化によるシグナル伝達制御」生化学会
    • Place of Presentation
      京都国際会館
    • Year and Date
      2011-09-21
    • Related Report
      2011 Final Research Report
  • [Presentation] アクチンADPリボシル化の構造基盤2011

    • Author(s)
      津下英明
    • Organizer
      生化学会
    • Place of Presentation
      京都国際会館(招待講演)
    • Year and Date
      2011-09-21
    • Related Report
      2011 Annual Research Report
  • [Presentation] 感染症因子とヒトタンパク質の相互作用を見る2011

    • Author(s)
      津下英明
    • Organizer
      X線の会
    • Place of Presentation
      阪急グランドビル26階
    • Year and Date
      2011-09-10
    • Related Report
      2011 Final Research Report
  • [Presentation] 感染症因子とヒトタンパク質の相互作用を見る2011

    • Author(s)
      津下英明
    • Organizer
      X線の会
    • Place of Presentation
      阪急グランドビル(招待講演)
    • Year and Date
      2011-09-10
    • Related Report
      2011 Annual Research Report
  • [Presentation] Structural basis for the Helicobacter pylori-carcinogenic TNF-alpha-inducing protein2011

    • Author(s)
      Tsurumura T., Tsuge H
    • Organizer
      国際結晶学会
    • Place of Presentation
      国際結晶学会Madrid
    • Related Report
      2011 Final Research Report
  • [Presentation] Crystal structure of Ia-Actin complex with novel ligand2011

    • Author(s)
      Tsurumura T., Tsuge H
    • Organizer
      国際結晶学会
    • Place of Presentation
      Madrid
    • Related Report
      2011 Final Research Report
  • [Presentation] ADPリボシル化毒素によるアクチン認識の特異性解析2011

    • Author(s)
      鶴村俊治、津下英明
    • Organizer
      日本蛋白質科学会
    • Place of Presentation
      大阪府吹田市
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] Crystal structure of Ia-Actin complex with novel ligand2011

    • Author(s)
      Tsurumura T., Tsuge H.
    • Organizer
      IUCr(国際結晶学会)
    • Place of Presentation
      Madrid Spain
    • Related Report
      2011 Annual Research Report
  • [Presentation] Structural basis for the Helicobacter pylori-carcinogenic TNF-alpha-inducing protein2011

    • Author(s)
      Tsurumura T., Tsuge H.
    • Organizer
      IUCr,(国際結晶学会)
    • Place of Presentation
      Madrid Spain
    • Related Report
      2011 Annual Research Report
  • [Presentation] 高度好熱菌HB8由来のフラビン還元酵素の構造機能解析ビタミンB研究委員会2010

    • Author(s)
      今川貴仁、津下英明
    • Organizer
      第422回研究協議会
    • Place of Presentation
      京都市
    • Year and Date
      2010-11-27
    • Related Report
      2011 Final Research Report
  • [Presentation] モノADPリボシル化毒素とその標的タンパク質アクチンとの複合体のX線結晶構造解析2010

    • Author(s)
      津下英明
    • Place of Presentation
      国立がんセンター研究所
    • Year and Date
      2010-02-22
    • Related Report
      2011 Final Research Report
  • [Presentation] 細菌およびウィルス感染症の構造生物学2010

    • Author(s)
      津下英明
    • Organizer
      第4回学術フロンティアシンポジウム「X線結晶構造解析と質量分析による生理活性蛋白質の構造機能相関の研究」
    • Place of Presentation
      徳島文理大学
    • Year and Date
      2010-01-30
    • Related Report
      2011 Final Research Report
  • [Presentation] 「X線結晶構造解析と質量分析による生理活性タンパク質の構造機能相関の研究」『細菌およびウィルス感染症の構造生物学』2010

    • Author(s)
      津下英明
    • Organizer
      第4回学術フロンティアシンポジウム
    • Place of Presentation
      徳島文理大学 徳島校 (徳島市)
    • Year and Date
      2010-01-30
    • Related Report
      2009 Annual Research Report
  • [Presentation] インフルエンザウィルスRNAポリメラーゼPB2のX線結晶構造解析2009

    • Author(s)
      津下英明
    • Organizer
      第416回ビタミンB研究協議会
    • Place of Presentation
      京都学園大学(京都府亀岡市)
    • Year and Date
      2009-05-29
    • Related Report
      2009 Annual Research Report
  • [Presentation] Structural Basis of influenza A virus RNA polymerase PB2 domain including pathogenicity determinant residue K6272009

    • Author(s)
      Tsuge H.
    • Organizer
      21^<th> IUBMB & 12^<th> FAOBMB International Congress of Biochemistry and Molecular Biology
    • Place of Presentation
      Shanghai, CHINA
    • Related Report
      2009 Annual Research Report
  • [Presentation] Crystal structure of influenza virus RNA polymerase PB2 including host determinant residue K6272009

    • Author(s)
      津下英明
    • Organizer
      第47回日本生物物理学会年会
    • Place of Presentation
      アスティとくしま(徳島市)
    • Related Report
      2009 Annual Research Report
  • [Presentation] Structural basis of the influenza A virus RNA polymerase PB2 RNA-binding domain containing the pathogenicity-determinant lysine 627 residue2009

    • Author(s)
      Kuzuhara T., Tsuge H.
    • Organizer
      第47回日本生物物理学会年会
    • Place of Presentation
      アスティとくしま(徳島市)
    • Related Report
      2009 Annual Research Report
  • [Remarks]

    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://www.cc.kyoto-su.ac.jp/~tsuge/Home_Japanese.html

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.cc.kyoto-su.ac.jp/-tsuge/Home_Japanese.html

    • Related Report
      2010 Annual Research Report
  • [Remarks] ホームページ

    • URL

      http://inetsrv103.bunri-u.ac.jp/kenkou/

    • Related Report
      2009 Annual Research Report

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Published: 2009-03-31   Modified: 2016-04-21  

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