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2006 Fiscal Year Final Research Report Summary

Structural study for the recognition mechanism of the target protein by a novel calcium sensor

Research Project

Project/Area Number 17570095
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

SHIMIZU Toshiyuki  Yokohama City University, International Graduate School of Arts and Sciences, Associate Professor, 国際総合科学研究科, 准教授 (30273858)

Project Period (FY) 2005 – 2006
KeywordsCHP / EF-hand / calcium / X-ray analysis / NHE1 / calcineurin / DRAK2
Research Abstract

Calcium ion plays significant role as a second messenger of intra cellular signaling in eukaryote. Rising concentration of intra cellar calcium is arisen by afflux of extra cellar calcium mediated by calcium channel and release of calcium from endoplasmic reticulum. Calcium binding protein binds to calcium and causes conformation change to modify down stream target molecules when intra cellar calcium rises.
CHP1 is comprised of 195 amino acids and shows substantial sequence similarity to the regulatory B subunit of calcineurin (CNB). Based on amino acid sequence CHP1 has 4 EF-hands (EF-1-4) that is known as calcium binding motif and N-myristoylation motif on its N-terminal..
CHP1 was also identified as a protein that interacts with intra cellar juxta-membrane region of Na+/H+ exchanger 1 (NHE1). CHP1 is essential for NHEls activity, and CHP1 binding defective mutant of NHE1 show a marked acidic shift of intra cellar pH. Furthermore, a mutant which displays lacking calcium-binding affinit … More y, also has a significantly reduced Na+/H+ exchange activity. Furthermore recent study reveals that CHP1 binds to DAPK related apoptosis inducing kinase 2 (DRAK2) and inhibits its kinase activity. CHP1 significantly reduced (〜85% inhibition) the kinase activity of DRAK2 for both autophosphorylation and phsphorylation of exogenous substrate. DRAK2 is a Ser/Thr kinase consisting of 371 amino acids and mainly consists of kinase domain (residues 33-293) The enzyme activity of some members of DAP kinase family is regulated via binding of calmodulin to a calmodulin binding region It is interesting that calcium and CHP1 negatively regulate the kinase activity of DRAK2 required for apoptotic induction.
CHP1 binding regions of NHE1 and DRAK2 have low similarity, so CHP1 may interact with multiple target on multiple manner. Despite the great importance of multiple intracellular functions of CHP1, no structural information of CHP1 has been obtained. In this study we performed X-ray crystallographic analysis of CHP1 to clarify CHP1s target recognition mechanism. We also perform crystallization of DRAK2. Less

  • Research Products

    (15 results)

All 2006 2005

All Journal Article (15 results)

  • [Journal Article] A pentatricopeptide repeat protein is a site-recognition factor in chloroplast RNA editing2006

    • Author(s)
      Okuda et al.
    • Journal Title

      J. Biol.Chem. 281

      Pages: 37661

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The common phospholipid binding activity of the N-terminal domains of PEX1 and VCP / p972006

    • Author(s)
      Shiozawa et al.
    • Journal Title

      FEBS J. 273

      Pages: 4959

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Crystallization and preliminary X-ray crystallographic studies of transportin 1 in complex with nucleocytoplasmic shuttling and nuclear localization fragments2006

    • Author(s)
      Imasaki et al.
    • Journal Title

      Acta Crystallogr. F62

      Pages: 785

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Structural basis for histone N-terminal recognition by human peptidylarginine deiminase 42006

    • Author(s)
      Arita et al.
    • Journal Title

      Proc. Natl. Acad. Sci., USA 103

      Pages: 5291

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A pentatricopeptide repeat protein is a site-recognition factor in chloroplast RNA editing2006

    • Author(s)
      Okuda, K et al.
    • Journal Title

      J.Biol.Chem. 281

      Pages: 37661-37667

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The common phospholipid binding activity of the N-terminal domains of PEX1 and VCP / p972006

    • Author(s)
      Shiozawa K et al.
    • Journal Title

      FEBSJ 273

      Pages: 4959-4971

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Crystallization and preliminary X-ray crystallographic studies of transportin 1 in complex with nucleocytoplasmic shuttling and nuclear localization fragments2006

    • Author(s)
      Imasaki et al.
    • Journal Title

      Acta Cryst. F62

      Pages: 785-78

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Structural basis for histone N-terminal recognition by human peptidylarginine deiminase 42006

    • Author(s)
      Arita et al.
    • Journal Title

      Proc.Natl.Acad Sci. USA 103

      Pages: 5291-5296

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Structural characterization of calcineurin B homologous protein 1.2005

    • Author(s)
      Naoe et al.
    • Journal Title

      J. Biol.Chem. 280

      Pages: 32372

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Crystallization and preliminary X-ray crystallographic analysis of rat calcineurin B homologous protein 12005

    • Author(s)
      Naoe et al.
    • Journal Title

      Acta Crystallogr. F61

      Pages: 612

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Structural characterization of calcineurin B homologous protein 1.2005

    • Author(s)
      Naoe et al.
    • Journal Title

      J.Biol.Chem. 280

      Pages: 32372-32378

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The first crystal structure of a family 31 carbohydrate-binding module with affinity to beta-1,3-xylan.2005

    • Author(s)
      Hashimoto et al.
    • Journal Title

      FEBS Lett. 579(20)

      Pages: 4324-4328

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Crystallization and preliminary X-ray crystallographic analysis of rat calcineurin B homologous protein 12005

    • Author(s)
      Naoe et al.
    • Journal Title

      Acta Crystallogr F61

      Pages: 612-613

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Crystal structures of type II restriction endonuclease Eco0109I and its complex with cognate DNA.2005

    • Author(s)
      Hashimoto et al.
    • Journal Title

      J.Biol.Chem. 280(7)

      Pages: 5605-10

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Crystal structure of the protein histidine phosphatase SixA in the multistep His-Asp phosphorelay.2005

    • Author(s)
      Hamada et al.
    • Journal Title

      Genes Cells 10(1)

      Pages: 1-11

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2008-05-27  

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