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Structural analysis of PLN/SERCA regulatome toward understanding of the mechanism of Ca2+-regulation in the cardiac muscle cells

Research Project

Project/Area Number 25291012
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Structural biochemistry
Research InstitutionThe University of Tokyo

Principal Investigator

Ogawa Haruo  東京大学, 分子細胞生物学研究所, 准教授 (40292726)

Project Period (FY) 2013-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2015: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
Keywords膜蛋白質 / イオンポンプ蛋白質 / X線結晶解析 / X線結晶構造解析
Outline of Final Research Achievements

SR calcium uptake is mediated by a SERCA2a, whose activity is reversibly regulated by its direct mediator phospholamban (PLN). PLN is the most important mediator of β adrenergic signal, and it controls SERCA2a depending on its phosphorylation state. Recently many regulators that controls the PLN/SERCA2a complex was discovered. They are thought to form a large-scale complex (PLN/SERCAa regulatome). However, due to lack of efficient expression/purification system for SERCA2/PLN, the details of the mechanisms how they regulate PLN/SERCAa complex is unclear. Thus, we aimed to elucidate the mechanism of regulation of PLN/SERCA2a by regulators with using our own large expression and purification system.

Report

(5 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (23 results)

All 2017 2016 2015 2014 2013

All Journal Article (8 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 2 results) Presentation (15 results) (of which Int'l Joint Research: 2 results,  Invited: 4 results)

  • [Journal Article] Genotype-phenotype correlations of malignant hyperthermia and central core disease mutations in the central region of the RYR1 channel.2016

    • Author(s)
      Murayama, T., Kurebayashi, N., Ogawa, H., Yamazawa, T., Oyamada, H., Suzuki, J., Kanemaru, K., Oguchi, K., Iino, M. and Sakurai, T.
    • Journal Title

      Hum Mutat.

      Volume: 37 Issue: 11 Pages: 1231-1241

    • DOI

      10.1002/humu.23072

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sequential substitution of K+ bound to Na+,K+-ATPase visualized by X-ray crystallography2015

    • Author(s)
      Ogawa, H., Cornelius, F., Hirata, A., Toyoshima, C.
    • Journal Title

      Nat Commun.

      Volume: 6 Issue: 1 Pages: 8004-8004

    • DOI

      10.1038/ncomms9004

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Functional analysis of SERCA1b, a highly expressed SERCA1 variant in myotonic dystrophy type 1 muscle2015

    • Author(s)
      Zhao, Y., Ogawa, H., Yonekura, S., Mitsuhashi, H., Mitsuhashi, S., Nishino, I., Toyoshima, C., Ishiura, S.
    • Journal Title

      Biochim. Biophys. Acta.

      Volume: 1852 Issue: 10 Pages: 2042-2047

    • DOI

      10.1016/j.bbadis.2015.07.006

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Biselyngbyasides, Cytotoxic Marine Macrolides, are Novel and Potent Inhibitors of the Ca2+ Pumps with a Unique Mode of Binding2015

    • Author(s)
      Morita, M., Ogawa, H., Ohno, O., Yamori, T., Suenaga, K., Toyoshima, C.
    • Journal Title

      FEBS Lett.

      Volume: 589 Issue: 13 Pages: 1406-1411

    • DOI

      10.1016/j.febslet.2015.04.056

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stimulation, inhibition or stabilization of Na, K-ATPase caused by specific lipid interactions at distinct sites2015

    • Author(s)
      M. Habeck, H. Haviv, A. Katz, E. Kapri-Pardes, S. Ayciriex, A. Shevchenko, H. Ogawa, C. Toyoshima, and S.J.D. Karlish
    • Journal Title

      J. Biol. Chem.

      Volume: 290 Issue: 8 Pages: 4829-4842

    • DOI

      10.1074/jbc.m114.611384

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ナトリウムポンプ蛋白質がナトリウムを選択的に運搬する機構 - How the Na+-pump recognizes and transports Na+ selectively.2015

    • Author(s)
      小川治夫, 金井隆太, 豊島近
    • Journal Title

      医学のあゆみ

      Volume: 254 Pages: 1186-1187

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Crystal structure of a Na^+-bound Na^+, K^+-ATPase preceding the E1P state.2013

    • Author(s)
      R. Kanai, H. Ogawa, B. Vilsen, F. Cornelius and C. Toyoshima
    • Journal Title

      Nature

      Volume: 502 Issue: 7470 Pages: 201-206

    • DOI

      10.1038/nature12578

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Crystal structures of the calcium pump and sarcolipin in the E1·Mg2+ state.2013

    • Author(s)
      C. Toyoshima
    • Journal Title

      Nature

      Volume: 495 Issue: 7440 Pages: 260-264

    • DOI

      10.1038/nature11899

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] Recent advances in structural studies of SR Ca2+-ATPase2017

    • Author(s)
      小川治夫
    • Organizer
      第94回日本生理学会
    • Place of Presentation
      浜松アクトシティコングレスセンター(静岡県浜松市)
    • Year and Date
      2017-03-28
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Large-scale production of mammalian membrane proteins toward determination of high resolution structures2017

    • Author(s)
      Haruo Ogawa, Chikashi Toyoshima
    • Organizer
      Biophysical Society 61st Annual Meeting
    • Place of Presentation
      New Orleans, Louisiana, USA
    • Year and Date
      2017-02-11
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Ca2+-ポンプ構造研究の最前線2016

    • Author(s)
      小川治夫、樺島佳樹、豊島近
    • Organizer
      日本生体エネルギー研究会 第42回討論会
    • Place of Presentation
      名古屋工業大学4号館ホール(愛知県名古屋市)
    • Year and Date
      2016-12-19
    • Related Report
      2016 Annual Research Report
  • [Presentation] 高分解能構造解析へ向けた哺乳類由来膜蛋白質の大量生産2016

    • Author(s)
      小川治夫、村山尚、呉林なごみ、豊島近
    • Organizer
      第89回 日本生化学会大会シンポジウム
    • Place of Presentation
      仙台国際センター/東北大学川内北キャンパス(宮城県仙台市)
    • Year and Date
      2016-09-25
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Kinetics by X-ray crystallography:sequential substitution of K+ bound to Na+,K+-ATPase2016

    • Author(s)
      Haruo Ogawa, Flemming Cornelius,Ayami Hirata, Chikashi Toyoshima
    • Organizer
      Biophysical Society 60th annual meeting
    • Place of Presentation
      Los Angeles Convention center, Los Angeles, California (USA)
    • Year and Date
      2016-02-27
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] X線結晶構造解析によるキネティックス測定:Na+,K+-ATPaseに結合したK+は段階的に置換される2015

    • Author(s)
      小川治夫, 平田絢美, Flemming Cornelius, 豊島近
    • Organizer
      日本生体エネルギー研究会 第41回討論会
    • Place of Presentation
      東京大学医学部1号館講堂(東京都・文京区)
    • Year and Date
      2015-12-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] Kinetics by X-ray crystallography: sequential substitution of K+ bound to Na+,K+-ATPase.2015

    • Author(s)
      Haruo Ogawa, Flemming Cornelius,Ayami Hirata, Chikashi Toyoshima
    • Organizer
      BMB2015(第38回日本分子生物学会 第88回日本生化学会合同大会)ワークショップ
    • Place of Presentation
      神戸ポートアイランド(兵庫県・神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Sequential substitution of bound K+ in the transmembrane binding sites of Na+,K+-ATPase, kinetics by X-ray crystallography.2015

    • Author(s)
      Haruo Ogawa, Flemming Cornelius,Ayami Hirata, Chikashi Toyoshima
    • Organizer
      日本生物物理学会第53回年会シンポジウム
    • Place of Presentation
      金沢大学 角間キャンパス自然科学本館(石川県・金沢市)
    • Year and Date
      2015-09-13
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] X-線結晶構造解析が明かすビセリングビアサイド類のCa2+ポンプ阻害機構2015

    • Author(s)
      森田 真布, 小川 治夫, 杖田 淳子, 大野 修, 矢守 隆夫, 豊島 近, 末永 聖武
    • Organizer
      日本化学会第95春季年会2015
    • Place of Presentation
      日本大学理工学部船橋キャンパス/薬学部(千葉県船橋市)
    • Year and Date
      2015-03-26 – 2015-03-29
    • Related Report
      2014 Annual Research Report
  • [Presentation] X-ray crystallographic study of Na,K-ATPase in complex with cardiotonic steroids2015

    • Author(s)
      Haruo Ogawa, Kanna Motoyama, Flemming Cornelius, Bente Vilsen, Chikashi Toyoshima
    • Organizer
      Biophysical Society 59th Annual meeting
    • Place of Presentation
      Baltimore Convention Center, Baltimore, MD, USA
    • Year and Date
      2015-02-07 – 2015-02-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] Na+,K+-ATPaseと強心配糖体複合体のX線結晶構造解析2014

    • Author(s)
      小川 治夫, 元山 かん奈, Cornelius Flemming, Vilsen Bente, 豊島 近
    • Organizer
      第87回日本生化学会
    • Place of Presentation
      京都国際会館(京都府京都市)
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] 筋強直性ジストロフィーの病態に関わる筋小胞体Ca2+-ATPase 1スプライスバリアントの機能的差異2014

    • Author(s)
      趙 一夢, 小川 治夫, 米倉 慎一郎, 三橋 弘明, 豊島 近, 石浦 章一
    • Organizer
      第87回日本生化学会
    • Place of Presentation
      京都国際会館(京都府京都市)
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] Large Production of SERCA toward determination of three-dimensional structures2014

    • Author(s)
      Haruo Ogawa, Yimeng Zhao, Ayami Hirata, Junko Tsueda, Shoichi Ishiura, Giuseppe Inesi, Chikashi Toyoshima
    • Organizer
      ASMB special symposia series, Na,K-ATPase and related transport ATPases: Structure, Mechanism, Cell Biology, Health and Disease
    • Place of Presentation
      De Werelt Conference Centre, Lunteren, Netherlands
    • Year and Date
      2014-08-30 – 2014-09-05
    • Related Report
      2014 Annual Research Report
  • [Presentation] Extensive analysis on the interaction between sarcolipin and Ca2+-ATPase2013

    • Author(s)
      Ogawa, H., Iwasawa, S., Hirata, A., Tsueda, J., Toyoshima, C.
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] Large production of mammalian membrane proteins toward determination of three-dimensional structures2013

    • Author(s)
      Ogawa, H., Hirata, A., Tsueda, J., Inesi, G., Toyoshima, C.
    • Organizer
      The 2nd HD Physiology International Symposium
    • Place of Presentation
      丸の内 My Plaza Hall
    • Related Report
      2013 Annual Research Report

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Published: 2013-05-21   Modified: 2019-07-29  

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