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Protein-protein interaction in intracellular signal transduction

Research Project

Project/Area Number 10179104
Research Category

Grant-in-Aid for Scientific Research on Priority Areas (A)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionHokkaido University (1999-2001)
Tokyo Metropolitan Organization for Medical Research (1998)

Principal Investigator

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

Co-Investigator(Kenkyū-buntansha) TSUKITA Shoichiro  Kyoto University, professor, 大学院・医学研究科, 教授 (50155347)
YAMAMOTO Tadashi  Tokyo University, professor, 医科学研究所, 教授 (40134621)
TAKENAWA Tadaomi  Tokyo University, professor, 医科学研究所, 教授 (40101315)
KOHDA Daisuke  Kyushu University, professor, 生体防御医学研究所・バイオサイエンス研究, 教授 (80186618)
HAKOSHIMA Toshio  Nara Institute of Science and Technology, professor, バイオサイエンス研究科, 教授 (00164773)
嶋田 一夫  東京大学, 大学院・薬学系研究科, 教授 (70196476)
貝淵 弘三  奈良先端科学技術大学院大学, バイオサイエンス研究科, 教授 (00169377)
Project Period (FY) 1998 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥131,800,000 (Direct Cost: ¥131,800,000)
Fiscal Year 2001: ¥30,700,000 (Direct Cost: ¥30,700,000)
Fiscal Year 2000: ¥34,600,000 (Direct Cost: ¥34,600,000)
Fiscal Year 1999: ¥31,900,000 (Direct Cost: ¥31,900,000)
Fiscal Year 1998: ¥34,600,000 (Direct Cost: ¥34,600,000)
KeywordsVav / SH3 / Grb2 / praline rich region / tertiary structure IP3 / radixin / IP3 / PTB様ドメイン / Vav-nSH3 / PRR / Grb2-cSH3 / バキュロウィルス / 多核体病ウィルス / Rho / N-WASP / NMR / X線結晶構造解析 / タイトジャンクション / 好中級活性酸素発生系 / PBI / PB2 / Neurop
Research Abstract

Vav is a guanine nucleotide exchange factor for the Rho/Rac family that is expressed exclusively in hematopoietic cells. Growth factor receptor-bound protein 2 (Grb2) has been proposed to play important roles in the membrane localization and activation of Vav through dimerization of its C-terminal Srchomology 3 (SH3) domain (GrbS) and the N-terminal SH3 domain of Vav (VavS). The crystal strucuture of VavS complexed with GrbS has been solved. VavS is distinct from other SH3 domain proteins in that its binding site for proline-rich peptides is blocked by its own RT loop. One of the ends of the VavS β-barrel forms a concave hydrophobic surface. The GrbS components make a contiguous complementary interface with the VavS surface. The binding site of GrbS for VavS partially overlaps with the canonical binding site for proline-rich peptides, but is definitely different. Mutations at the interface caused a decrease in the binding affinity of VavS for GrbS by 4- to 40-fold. The structure reveals how GrbS discriminates VavS specifically from other signaling molecules without binding to the proline-rich motif.

Report

(5 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (40 results)

All Other

All Publications (40 results)

  • [Publications] Ponting, C.P.: "OPR, PC and AID : all in the PB1 family"TIBS. 27. 10 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ogura, K.: "Solution structure of N-terminal SH3 domain of Vav and the recognition site for Grb2 C-terminal SH3 domain"J.Biomol.NMR. 22. 37-46 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kawasaki, M.: "Random PCR-Based screening for soluble domains using green fluorescent protein"Biochem.Biophys.Res.Commun.. 280. 842-844 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Terasawa, H.: "Structure and ligand recognition of the PB1 domain : A novel protein Modulebinding to the PC motif"The EMBO J.. 20. 3947-3956 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nishida, M.: "Novel recognition mode between Vav and Grb2 SH3 domains"The EMBO J.. 20. 2995-3007 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yuzawa, S: "Solution structure of Grb2 reveals extensive flexibility for target recognition"J.Mol.Biol.. 306. 527-537 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Panting, C. P., Ito, T., Moscat, J., Diaz-Mew, M., Inagaki, F., Sumimoto, H.: "OPR, PC and AID : all in the PB1 femily"TIBS. 27. 10 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ogura, K., Nagata, K., Horiuchi, M., Ebisui, E., Hasuda, T., Yuzawa, S., Nishida, M., Hatanaka, H., Inagaki, F.: "Solution structure of N-terminal SH3 domain of Vav and the recognition site for Grb2 C-terminal SH3 domain"J. Biomal. NMR. 22. 37-46 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Terasawa, H., Noda, Y., Ito, T., Hatanaka, H., Ichikawa, S., Ogura, K., Sumimoto, H., Inagaki, F.: "Structure and ligand recognition of the PBI domain : A novel protein modulebinding to the PC motif"EMBO J., 20. 15. 3947-3956 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nishida, M., Nagata, K., Hachimori, Y., Horiuchi, M., Ogura, Mandiyan, K. V., Schlessinger, J., Inagaki, F.: "Novel recognition mode between Vav and Grb2 SH3 domains"EMBO J. 20. 12. 2995-3007 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kawasaki, M, Inagaki, F.: "Random PCR-Based screening for soluble domains using green fluorescent protein"Biochem. Biophys. Res. Commun.. 280, 3. 842-844 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yuzawa, S., Yokochi, M., Hatanaka, H., Ogura, K., Kataoka, M., Miura, K., Mandiyan, K. V., Schlessinger, J., Inagaki, F.: "Solution structure of Grb2 reveals extensive flexisibility necessary for recognition"J. Mol. Biol.. 306. 527-537 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ponting, C.P.: "OPR, PC and AID : all in the PB1 family"TIBS. 27. 10 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ogura, K.: "Solution structure of N-terminal SH3 domain of Vav and the recognition site for Grb2 C-terminal SH3 domain"J. Biomol. NMR. 22. 37-46 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kawasaki, M.: "Random PCR-Based screening for soluble domains using green fluorescent protein"Biochem. Biophys. Res. Commun.. 280. 842-844 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Terasawa, H.: "Structure and ligand recognition of the PB1 domain : A novel protein Modulebinding to the PC motif"The EMBO J.. 20. 3947-3956 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nishida, M.: "Novel recognition mode between Vav and Grb2 SH3 domains"The EMBO J.. 20. 2995-3007 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yuzawa, S: "Solution structure of Grb2 reveals extensive flexibility for target recognition"J. Mol. Biol.. 306. 527-537 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kawasaki,M.: "Random PCR-based screening for soluble domains using green fluorescent protein."Biochem.Biophys.Res.Commun.. 280. 842-844 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yuzawa,S.: "Solution structure of Grb2 reveals extensive flexibility for target recognition."J.Mol.Biol.. 306. 527-537 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Muto,T.: "NMR Identification of the Tom20 Binding Segment in Mitochondrial Presequences."J.Mol.Biol.. 306. 137-143 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hamada,K.: "Structural basis of the membrane-targeting and unmasking mechanisms of ERM proteins revealed by the structure of the radixin FERM domain."EMBO J.. 19(17). 4449-4462 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kawakami,T.: "Polypeptide Synthesis Using an Expressed Peptide as a Building Block via the Thioester Method."Tetrahedron Letters. 41(15). 2625-2628 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takahashi,H.: "A Novel NMR Method for the Determination of the Interface of Large Protein-protein Complexes."Nature Struct.Biol.. 7. 220-223 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 箱嶋敏雄: "実験医学増刊号18(18(竹縄忠臣 編)"分子複合体のX線結晶構造解析、「次世代のシグナル蛋白質研究:プロテオーム研究とシグナル蛋白ドメイン」. 7 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Miki H.: "WAVE, a novel WASP-family protein involved in actin reorganization induced by Rac"EMBO J.. 17. 6932-6941 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Maesaki R.: "The structural basis of Rho effector recognition revealed by the crystal structure of human RhoA complexed with the effector domain of PKN/PRK1"Mol Cell.. 4・5. 793-803 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hirotsu S.: "Crystal structure of a multifunctional 2-Cys peroxiredoxin heme-binding protein 23 kDa/proliferation-associated gene product"Proc Natl Acad Sci U S A. 96・22. 12333-12338 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ogura K.: "Solution structure of human acidic fibroblast growth factor and interaction with heparin-derived hexasaccharide"J.Biomol.NMR. 13. 11-24 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ogura K.: "Solution structure of the SH2 Domain of Grb2 Complexed with the Shc-derived Phosphotyrosine-containing Peptide"J.Mol.Biol.. 289. 439-445 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Koga, H.: "Tetratricopeptide repeat (TPR) mitifs of p67 (phox) participate in interaction with the small GTPase Rc and activation of the phagocyte NADPH oxidase"J. Biol. Chem.. 274・35. 25051-25060 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 湯沢 聡: "細胞工学"Grb2の柔軟な構造に見る巧みな結合様式. 8 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 神田 大輔: "蛋白質核酸酵素"細胞増殖因子とレセプターの構造生物. 9 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ichikawa,S.: "Solution Structure of Derf 2,the major mite allergen for atopic diseases." J.Biol.Chem.273. 356-360 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ogura,K.: "Solution structure of human acldic fibroblast growth factor and interaction with heparin-derived hexasaccharide." J.Biomol.NMR. 13. 11-24 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Matsui,T.: "Rho-kinase phosphorylates COOH-terminal threonines of ezrin/radixin/moesin(ERM)proteins and regulates their head-to-tail association." J.Cell Biol.140. 647-657 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kuroda,S.: "Role of IQGAP1,a target of the small GTPases Cdc42 and Rac1,in the regulation of E-cadherin-mediated cell-cell adhesion." Science. 281. 832-835 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Abe,Y.: "Disulfide bond structure of human epidermal growth factor Receptor." J.Biol.Chem.273. 11150-11157 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Miki,H.: "Induction of filopodium formation by a WASP-related actin-depolymerizing protein N-WASP." Nature. 391. 93-96 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 稲垣冬彦: "SH2、SH3の構造生物学.(蛋白質 核酸 酵素増刊号「構造生物学のフロンティア」)" 共立出版(株), 13(630) (1999)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2018-03-28  

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