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Mechanism in Energy Transduction of Ca^<2+> Pump and Molecular Basis of Related Genetic Diseases

Research Project

Project/Area Number 16370066
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biophysics
Research InstitutionAsahikawa Medical College

Principal Investigator

SUZUKI Hiroshi  Asahikawa Medical College, School of Medicine, Professor, 医学部, 教授 (50183421)

Co-Investigator(Kenkyū-buntansha) DAIHO Takashi  Asahikawa Medical College, School of Medicine, Assistant Professor, 医学部, 助教授 (90207267)
YAMASAKI Kazuo  Asahikawa Medical College, School of Medicine, Research Associate, 医学部, 助手 (60241428)
KATO Sanae  Asahikawa Medical College, School of Medicine, Research Associate, 医学部, 助手 (80291061)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥15,200,000 (Direct Cost: ¥15,200,000)
Fiscal Year 2005: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥11,600,000 (Direct Cost: ¥11,600,000)
KeywordsCa^<2+> pump / Ca^<2+>-ATPase / Sarco(endo)plasmic reticulum / Darier disease / Hailey-Hailey disease / Golgi apparatus / Ca^<2+> / Mn^<2+> pump / Mn^<2+>-ATPase / カルシウムポンプ / SEARCA / Ca^<2+>輸送 / リン酸化中間体 / 疎水性相互作用 / Caホメオスタシス
Research Abstract

Sarco(endo)plasmic reticulum Ca^<2+>-ATPases is the representative members of P-type ATPase family and catalyze Ca^<2+> transport coupled with ATP hydrolysis. The Ca^<2+>-ATPase consists of the three cytoplasmic domains (Nucleotide binding (N), Phosphorylation (P), and Actuator (A)) and ten transmembrane helices (M1〜M10, or eleven M11 in the SERCA2b isoform). The Ca^<2+>-ATPase forms an auto-phosphorylated intermediate (EP) during the transport cycle.
In this research, we revealed and found the followings :
1)The large motions of the cytoplasmic three domains and the changes in their interactions take place during the Ca^<2+> transport cycle.
2)The large rotation of the A domain and its tight association with the P domain take place for the isomerization of EP (i.e.E1P to E2P isomerization).
3)The strong interactions at the two specific regions of the A-P domain interface in E2P are critical for the Ca^<2+> release into the lumen and also critical for the E2P hydrolysis after the Ca^<2+> release. We could identify the structural elements involved in these domain-motions and -interactions and reveal their actual roles in the Ca^<2+>-transport.
4)We developed successfully the stable structural analogs of the phosphorylated intermediates and revealed their characteristic properties, hence contributed to their atomic level structural studies.
5)We revealed the molecular defects of SERCA2b associated with the Darier-disease causing 51 mutations in the 51 pedigrees (most of the substitutions and deletions of residues reported so far).
6)We found the specific expression and localization of the Golgi Ca^<2+>/Mn^<2+>-ATPase, another member of the P-type ATPase family, of which genetic defects causes Hailey-Hailey disease. We also predicted its function in the cell differentiation.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (38 results)

All 2006 2005 2004

All Journal Article (38 results)

  • [Journal Article] ATP2C1 is specifically localized in the basal layer of normal epidermis and its depletion triggers keratinocyte differentiation2006

    • Author(s)
      Masaki Yoshida
    • Journal Title

      Journal of Dermatological Science (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] ATP2C1 is specifically localized in the basal layer of normal epidermis and its depletion triggers keratinocyte differentiation2006

    • Author(s)
      Yoshida, M. et al.
    • Journal Title

      J.Dermatol Sci. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] ATP2C1 is specifically localized in the basal layer of normal epidermis and its depletion triggers keratinocyte differentiation2006

    • Author(s)
      Masaki Yoshida
    • Journal Title

      Journal of Dermatological Science (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Critical Hydrophobic Interactions between Phosphorylation and Actuator Domains of Ca^<2+>-ATPase for Hydrolysis of Phosphorylated Intermediate2005

    • Author(s)
      Guoli Wang
    • Journal Title

      The Journal of Biological Chemistry 280・28

      Pages: 26508-26516

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Ca^<2+> occlusion and de-occlusion at transport sites of phosphoenzyme intermediates of sarcoplasmic reticulum Ca^<2+>-ATPase studied by mutagenesis2005

    • Author(s)
      Takashi Daiho
    • Journal Title

      生化学 77・8

      Pages: 803-803

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Analysis of Ca^<2+>-release process in the phosphorylated intermediates of sarcoplasmic reticulum Ca^<2+>-ATPase by mutagenesis2005

    • Author(s)
      Kazuo Yamasaki
    • Journal Title

      生化学 77・8

      Pages: 804-804

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Stable analogs for phosphoenzyme intermediates of sarcoplasmic reticulum Ca-ATPase2005

    • Author(s)
      Stefania Danko
    • Journal Title

      生物物理 45・1

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Changes in Cytoplasmic Domain Organization and Energy Transduction in Calcium Pump2005

    • Author(s)
      Hiroshi Suzuki
    • Journal Title

      生物物理 45・1

      Pages: 16-21

    • NAID

      10015441996

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Changes in Cytoplasmic Domain Organization and Energy Transduction in Calcium Pump2005

    • Author(s)
      Suzuki, H. et al.
    • Journal Title

      SEIBUTSUBUTSURI 45(1)

      Pages: 16-21

    • NAID

      10015441996

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Stable analogs for phosphoenzyme intermediates of sarcoplasmic reticulum Ca-ATPase2005

    • Author(s)
      Danko, S. et al.
    • Journal Title

      SEIBUTSUBUTSURI 45(1)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Ca^<2+> occlusion and de-occlusion at transport sites of phosphoenzyme intermediates of sarcoplasmic reticulum Ca^<2+>-ATPase studied by mutagenesis2005

    • Author(s)
      Daiho, T. et al.
    • Journal Title

      SEIKAGAKU 77(8)

      Pages: 803-803

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Analysis of Ca^<2+>-release process in the phosphorylated intermediates of sarcoplasmic reticulum Ca^<2+>-ATPase by mutagenesis2005

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

      SEIKAGAKU 77(8)

      Pages: 804-804

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Critical hydrophobic interactions between phosphorylation and actuator domains of Ca^<2+>-ATPase for hydrolysis of phosphorylated intermediate2005

    • Author(s)
      Wang, G. et al.
    • Journal Title

      J.Biol.Chem. 280(28)

      Pages: 26508-26516

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Ca^<2+> occlusion and de-occlusion at transport sites of phosphoenzyme intermediates of sarcoplasmic reticulum Ca^<2+>-ATPase atudied by mutagenesis2005

    • Author(s)
      Takashi Daiho
    • Journal Title

      生化学 77・8

      Pages: 803-803

    • Related Report
      2005 Annual Research Report
  • [Journal Article] カルシウムポンプのドメイン間相互作用変化とエネルギー変換2005

    • Author(s)
      鈴木 裕
    • Journal Title

      生物物理 45・1

      Pages: 16-21

    • NAID

      10015441996

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Distinct type of Abnormality in Kinetic Properties of Three Darier Disease-causing Sarco(endo)plasmic Reticulum Ca^<2+>-ATPase(SERCA2b)Mutants2004

    • Author(s)
      Kazuo Yamasaki
    • Journal Title

      生化学 76・8

      Pages: 781-781

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Comprehensive and systematic analysis of function and expression of the 51 missense mutants of SERCA2b found in Darier's Disease patients2004

    • Author(s)
      Takashi Daiho
    • Journal Title

      生化学 76・8

      Pages: 781-781

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Essential Roles of Hydrophobic Interactions at the Interface of Gathered P and A Domains of Sarcoplasmic Reticulum Ca^<2+>-ATPase in Energy Transduction2004

    • Author(s)
      Guoli Wang
    • Journal Title

      生化学 76・8

      Pages: 781-781

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Distinct natures of Be/F-bound, Al/F-bound, and Mg/F-bound stable analogues of an ADP-insensitive phosphoenzyme intermediate of sarcoplasmic reticulum Ca^<2+>-ATPase2004

    • Author(s)
      Hiroshi Suzuki
    • Journal Title

      生化学 76・8

      Pages: 782-782

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Structure and function of Ca pump and the molecular basis of genetic diseases caused by its mutations2004

    • Author(s)
      Hiroshi Suzuki
    • Journal Title

      生物物理 44・1

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Distinct natures of beryllium fluoride-bound, aluminum fluoride-bound, and magnesium fluoride-bound stable analogues of an ADP-insensitive phosphoenzyme intermediate of sarcoplasmic reticulum Ca^<2+>-ATPase : changes in catalytic and transport sites during phosphoenzyme hydrolysis2004

    • Author(s)
      Stefania Danko
    • Journal Title

      The Journal of Biological Chemistry 279・15

      Pages: 14991-14998

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Distinct types of abnormality in kinetic properties of three Darier disease-causing sarco(endo)plasmic reticulum Ca^<2+>-ATPase mutants that exhibit normal expression and high Ca^<2+> transport activity2004

    • Author(s)
      Katsuhiko Sato
    • Journal Title

      The Journal of Biological Chemistry 279・34

      Pages: 35595-35603

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Multiple and Distinct Effects of Mutations of Tyr^<122>, Glu^<123>, Arg^<324>, and Arg^<334> Involved in Interactions between the Top Part of Second and Fourh Transmembrane Helices in Sarcoplasmic Reticulum Ca^<2+>-ATPase2004

    • Author(s)
      Kazuo Yamasaki
    • Journal Title

      The Journal of Biological Chemistry 279・3

      Pages: 2202-2210

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Distinct Natures of Beryllium Fluoride-bound, Aluminum Fluoride-bound, and Magnesium Fluoride-bound Stable Analogues of an ADP-insensitive Phosphoenzyme Intermediate of Sarcoplasmic Reticulum Ca^<2+>-ATPase : CHANGES IN CATALYTIC AND TRANSPORT SITES DURING PHOSPHOENZYME HYDROLYSIS2004

    • Author(s)
      Danko, S. et al.
    • Journal Title

      J.Biol.Chem. 279(15)

      Pages: 14991-14998

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Distinct types of abnormality in kinetic properties of three Darier disease-causing sarco(endo)plasmic reticulum Ca^<2+>-ATPase mutants that exhibit normal expression and high Ca^<2+> transport activity2004

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

      J.Biol.Chem. 279(34)

      Pages: 35595-35603

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Multiple and Distinct Effects of Mutations of Tyr^<122>,Glu^<123>,Arg^<324>, and Arg^<334> Involved in Interactions between the Top Part of Second and Fourth Transmembrane Helices in Sarcoplasmic Reticulum Ca^<2+>-ATPase.2004

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

      J.Biol.Chem. 279(3)

      Pages: 2202-2210

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Structure and function of Ca pump and the molecular basis of genetic diseases caused by its mutations2004

    • Author(s)
      Suzuki, H. et al.
    • Journal Title

      SEIBUTSUBUTSURI 44(1)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Distinct type of Abnormality in Kinetic Properties of Three Darier Disease-causing Sarco(endo)plasmic Reticulum Ca^<2+>-ATPase (SERCA2b) Mutants2004

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

      SEIKAGAKU 76(8)

      Pages: 781-781

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Comprehensive and systematic analysis of function and expression of the 51 missense mutants of SERCA2b found in Darier's Disease patients2004

    • Author(s)
      Daiho, T. et al.
    • Journal Title

      SEIKAGAKU 76(8)

      Pages: 781-781

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Essential Roles of Hydrophobic Interactions at the Interface of Gathered P and A Domains of Sarcoplasmic Reticulum Ca^<2+>-ATPase in Energy Transduction2004

    • Author(s)
      Wang, G et al.
    • Journal Title

      SEIKAGAKU 76(8)

      Pages: 781-781

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Distinct natures of Be/F-bound, Al/F-bound, and Mg/F-bound stable analogues of an ADP-insensitive phosphoenzyme intermediate of sarcoplasmic reticulum Ca^<2+>-ATPase2004

    • Author(s)
      Suzuki, H. et al.
    • Journal Title

      SEIKAGAKU 76(8)

      Pages: 782-782

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Distinct Types of Abnormality in Kinetic Properties of Three Darier Disease-causing Sarco(endo)plasmic Reticulum Ca2+-ATPase (SERCA2b) Mutants, Which Exhibit Normal Expression and High Ca^<2+> Transport Activity2004

    • Author(s)
      Katsuhiko Sato
    • Journal Title

      The Journal of Biological Chemistry 279・34

      Pages: 35595-35603

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Distinct Natures of Be/F-bound, Al/F-bound, and Mg/F-bound Stable Analogues of ADP-insensitive Phosphoenzyme Intermediate of Sarcoplasmic Reticulum Ca^<2+>-ATPase2004

    • Author(s)
      Stefania Danko
    • Journal Title

      The Journal of Biological Chemistry 279・15

      Pages: 14991-14998

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Multiple and Distinct Effects of Mutations of Tyr^<122>, Glu^<123>, Arg^<324>, and Arg^<334> Involved in Interactions between the Top Part of Second and Fourth Transmembrane Helices in Sarcoplasmic Reticulum Ca^<2+>-ATPase2004

    • Author(s)
      Kazuo Yamasaki
    • Journal Title

      The Journal of Biological Chemistry 279・3

      Pages: 2202-2210

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Caポンプの構造機能連関とその異常による病態2004

    • Author(s)
      鈴木 裕
    • Journal Title

      生物物理 44・S1

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Distinct Natures of Be/F-bound, Al/F-bound, and Mg/F-bound Stable Analogues of ADP-insensitive Phosphoenzyme Intermediate of Sarcoplasmic Reticulum Ca^<2+>-ATPase2004

    • Author(s)
      Hiroshi Suzuki
    • Journal Title

      生化学 76・8

      Pages: 782-782

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Comprehensive and systematic analysis of function and expression of the 51 missense mutants of SERCA2b found in Darier's patients2004

    • Author(s)
      Takashi Daiho
    • Journal Title

      生化学 76・8

      Pages: 781-781

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Distinct Types of Abnormality in Kinetic Properties of Three Darier Disease-causing Sarco(endo)plasmic Reticulum Ca^<2+>-ATPase(SERCA2b)Mutants2004

    • Author(s)
      Kazuo Yamasaki
    • Journal Title

      生化学 76・8

      Pages: 781-781

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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