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P-type pump ; Molecular basis of energy coupling and carcinogenesis caused by defects

Research Project

Project/Area Number 15H04346
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

Suzuki Hiroshi  旭川医科大学, 医学部, 教授 (50183421)

Co-Investigator(Kenkyū-buntansha) 山崎 和生  旭川医科大学, 医学部, 講師 (60241428)
安田 哲  旭川医科大学, 医学部, 助教 (80749896)
大保 貴嗣  旭川医科大学, 医学部, 准教授 (90207267)
Research Collaborator MASAIKE Tomoko  
MINOWA Osamu  
DANKO Stefania  
Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000)
Fiscal Year 2018: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2017: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2015: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
KeywordsCa-pump / active transport / flippase / energy coupling / P-type ATPase / Ca-ATPase / Caポンプ / 構造機能連関 / ENU-mutagenesis / 生物物理 / 酵素 / 生体分子 / 蛋白質 / 癌 / エネルギー共役 / リン酸化中間体 / Ca輸送 / 能動輸送 / 蛋白構造変化 / 発癌 / mutations / kinetics / Structure and Function / tumor
Outline of Final Research Achievements

Gating mechanism of sarco(endo)plasmic reticulum Ca-pump SERCA1a and involvement of lipid on membrane in the pump function were studied, thereby understanding of energy coupling mechanism in the active Ca2+ transport were further deepened. By the use of the Ca2+-pump, the methods for a single molecule dynamics were developed, and the structural changes of the pump were analyzed for understanding the structural mechanism. For the flippase, another P-type ATPase, studies were performed to identify its specific substrates, and reveal the mechanism. Fur types of mutations of endoplasmic Ca2+-pump SERCA2b that develop squamous cell carcinoma in mouse model were identified, and the pathological consequences and defects in the pump protein were revealed.

Academic Significance and Societal Importance of the Research Achievements

Caポンプの作動機序、即ち如何に構造が大きく変化し、如何なる構造領域が如何なる役割を果たし、ポンプ機能を成立させるかを「分子解剖学」により次々に露わにできた。またポンプ異常と病態脂質二重層形成機序の理解を深めると共に、さらに膜蛋白全般について作動機序解明の研究基盤を実例を持って形成した。
2017年度には、当該分野のほとんどすべての著名な、また若手の研究者を集め、滋賀県大津にて国際会議(P-type international meeting)を主催し、深い議論と交流の場を設け、国際交流と共に当該分野の今後の発展のため、また日本がその中心となって今後も深く貢献するための基盤さらに強くした。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (38 results)

All 2018 2017 2016 2015

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 5 results,  Acknowledgement Compliant: 4 results) Presentation (30 results) (of which Int'l Joint Research: 5 results,  Invited: 3 results) Book (2 results) Funded Workshop (1 results)

  • [Journal Article] Nanodisc-based kinetic assays reveal distinct effects of phospholipid headgroups on the phosphoenzyme transition of sarcoplasmic reticulum Ca2+-ATPase2017

    • Author(s)
      Yamasaki K, Daiho T, Danko S, Yasuda S, Suzuki H.
    • Journal Title

      Journal of Biological Chemistry

      Volume: 292 Issue: 49 Pages: 20218-20227

    • DOI

      10.1074/jbc.m117.816702

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Membrane Perturbation of ADP-insensitive Phosphoenzyme of Ca2+-ATPase Modifies Gathering of Transmembrane Helix M2 with Cytoplasmic Domains and Luminal Gating2017

    • Author(s)
      Stefania Danko, Kazuo Yamasaki1, Takashi Daiho1, and Hiroshi Suzuki
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 1-12

    • DOI

      10.1038/srep41172

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Glycine 105 as Pivot for a Critical Knee-like Joint between Cytoplasmic and Transmembrane Segments of Second Transmembrane Helix in Ca2+-ATPase2016

    • Author(s)
      Takashi Daiho1, Kazuo Yamasaki, Stefania Danko, and Hiroshi Suzuki
    • Journal Title

      The Journal of Biological Chemistry

      Volume: 291 Issue: 47 Pages: 24688-24701

    • DOI

      10.1074/jbc.m116.759704

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Novel allelic mutations in murine Serca2 induce differential development of squamous cell tumors.2016

    • Author(s)
      Toki H,Minowa O, Inoue M, Motegi H, Karashima Y, Ikeda A, Kaneda H, Sakuraba Y, Saiki Y, Wakana S, Suzuki H, Gondo Y, Shiroishi T, Noda T
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 476 Issue: 4 Pages: 175-182

    • DOI

      10.1016/j.bbrc.2016.04.136

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Assembly of a Tyr122 Hydrophobic Cluster in Sarcoplasmic Reticulum Ca2+-ATPase Synchronizes Ca2+ Affinity Reduction and Release with Phosphoenzyme Isomerization2015

    • Author(s)
      Yamasaki K., Daiho T., Danko S., and Suzuki H.
    • Journal Title

      Journal of Biological Chemistry

      Volume: 290 Issue: 46 Pages: 27868-27879

    • DOI

      10.1074/jbc.m115.693770

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 筋小胞体カルシウムポンプのCa2+結合に及ぼす界面活性剤の効果2018

    • Author(s)
      大保貴嗣、山崎和生、Danko Stefania、安田哲、鈴木裕
    • Organizer
      日本生化学会 第91回大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 筋小胞体Ca2+-ATPaseの脱共役モードについて2018

    • Author(s)
      山崎和生、大保貴嗣、Danko Stefania、安田哲、鈴木裕
    • Organizer
      日本生化学会 第91回大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] フリッパーゼATP8A1の反応と安定性に対する界面活性剤および脂質の影響2018

    • Author(s)
      安田哲、山崎和生、大保貴嗣、高津宏之、申惠媛、Danko Stefania、鈴木裕
    • Organizer
      日本生化学会 第91回大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 筋小胞体カルシウムポンプのCa2+結合に及ぼす界面活性剤の効果2018

    • Author(s)
      大保貴嗣、山崎和生、Danko Stefania、安田哲、鈴木裕
    • Organizer
      日本生体エネルギー研究会 第44回討論会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 筋小胞体Ca2+-ATPaseの脱共役モードについて2018

    • Author(s)
      山崎和生、大保貴嗣、Danko Stefania、安田哲、鈴木裕
    • Organizer
      日本生体エネルギー研究会 第44回討論会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ヒトフリッパーゼATP8A1の反応機構解析2018

    • Author(s)
      安田哲、山崎和生、大保貴嗣、高津宏之、申惠媛、Danko Stefania、鈴木裕
    • Organizer
      日本生体エネルギー研究会 第44回討論会
    • Related Report
      2018 Annual Research Report
  • [Presentation] デフォーカスイメージング法の確度評価とSERCA1a の構造変化検出に向けた試み2018

    • Author(s)
      加藤孝信、藤村章子、山崎和生、大保貴嗣、Danko Stefania、鈴木裕、西坂崇之
    • Organizer
      日本生体エネルギー研究会 第44回討論会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ナノディスク中の筋小胞体Ca2+-ATPaseに標識された単一蛍光分子の角度と明滅による中間体構造の評価2018

    • Author(s)
      竹村勁哉、山崎和生、大保貴嗣、Danko Stefania、小島知樹、鈴木裕、政池知子
    • Organizer
      日本生体エネルギー研究会 第44回討論会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Structure/function of Ca-ATPase revealed by mutations, kinetics, and structural analyses of reaction intermediates2017

    • Author(s)
      Hiroshi Suzuki, Takashi Daiho, Kazuo Yamasaki, Satoshi Yasuda, Stefania Danko
    • Organizer
      The 15th International ATPase Conference on “Na,K-ATPase and Related Transport ATPases”
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Novel allelic mutations in murine Serca2 induce differential development of squamous cell tumors2017

    • Author(s)
      Hideaki Toki, Osamu Minowa, Maki Inoue, Hiromi Motegi, Yuko Karashima, Ami Ikeda, Hideki Kaneda, Yoshiyuki Sakuraba, Yuriko Saiki, Shigeharu Wakana, Hiroshi Suzuki, Yoichi Gondo, Toshihiko Shiroishi, Tetsuo Noda
    • Organizer
      The 15th International ATPase Conference on “Na,K-ATPase and Related Transport ATPases”
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Glycine 105 as Pivot for a Critical Knee-like Joint between Cytoplasmic and Transmembrane Segments of the Second Transmembrane Helix in Ca2+-ATPase2017

    • Author(s)
      Takashi Daiho, Kazuo Yamasaki, Stefania Danko, Hiroshi Suzuki
    • Organizer
      The 15th International ATPase Conference on “Na,K-ATPase and Related Transport ATPases”
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Effects of phospholipid’s head groups on the properties of sarcoplasmic reticulum Ca2+-ATPase embedded in nanodisc2017

    • Author(s)
      Kazuo Yamasaki, Takashi Daiho, Stefania Danko, Satoshi Yasuda, Hiroshi Suzuki
    • Organizer
      The 15th International ATPase Conference on “Na,K-ATPase and Related Transport ATPases”
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Membrane Perturbation of ADP-insensitive Phosphoenzyme of Ca2+-ATPase Modifies Gathering of Transmembrane Helix M2 with Cytoplasmic Domains and Luminal Gating2017

    • Author(s)
      Stefania Danko, Kazuo Yamasaki, Takashi Daiho, and Hiroshi Suzuki
    • Organizer
      The 15th International ATPase Conference on “Na,K-ATPase and Related Transport ATPases”
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 筋小胞体カルシウムポンプの活性に対する界面活性剤の影響2017

    • Author(s)
      大保 貴嗣、山崎 和生、Stefania Danko、安田哲、鈴木 裕
    • Organizer
      生命科学系学会合同年次大会(第90回日本生化学会大会)
    • Related Report
      2017 Annual Research Report
  • [Presentation] ナノディスクに組み込んだ筋小胞体Ca2+-ATPaseの活性に対する膜表面電荷の影響2017

    • Author(s)
      山崎 和生、大保 貴嗣、Stefania Danko、安田哲、鈴木 裕
    • Organizer
      生命科学系学会合同年次大会(第90回日本生化学会大会)
    • Related Report
      2017 Annual Research Report
  • [Presentation] フリッパーゼの生化学的反応機構の解析2017

    • Author(s)
      安田哲、山崎 和生、大保 貴嗣、高津 宏之、申 惠媛、Stefania Danko、鈴木 裕
    • Organizer
      生命科学系学会合同年次大会(第90回日本生化学会大会)
    • Related Report
      2017 Annual Research Report
  • [Presentation] 筋小胞体カルシウムポンプの反応に及ぼす界面活性剤の効果2017

    • Author(s)
      大保 貴嗣、山崎和生、Stefania Danko、安田 哲、鈴木裕
    • Organizer
      日本生体エネルギー研究会 第43回討論会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 筋小胞体カルシウムポンプ活性に対する脂質ヘッドグループ及び 膜表面電荷の影響の解析2017

    • Author(s)
      山崎 和生、大保 貴嗣、Stefania Danko、安田哲、鈴木 裕
    • Organizer
      日本生体エネルギー研究会 第43回討論会
    • Related Report
      2017 Annual Research Report
  • [Presentation] フリッパーゼの反応機構解析2017

    • Author(s)
      安田哲、山崎 和生、大保 貴嗣、高津 宏之、申 惠媛、Stefania Danko、鈴木 裕
    • Organizer
      日本生体エネルギー研究会 第43回討論会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Caポンプのエネルギー共役;M2-helix膜貫通部分(M2m)と細胞質部分(M2c)をつなぐGly105の柔軟性の機能2016

    • Author(s)
      大保 貴嗣、山崎和生、Stefania Danko、鈴木裕
    • 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
    • Year and Date
      2016-12-19
    • Related Report
      2016 Annual Research Report
  • [Presentation] 脂質ヘッドグループが筋小胞体カルシウムポンプ活性に及ぼす影響―ナノディスク組み込み標品を用いて―2016

    • Author(s)
      山崎 和生、大保 貴嗣、Stefania Danko、鈴木 裕
    • 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
    • Year and Date
      2016-12-19
    • Related Report
      2016 Annual Research Report
  • [Presentation] Membrane Perturbation of ADP-insensitive Phosphoenzyme of Ca2+-ATPase Modifies Gathering of Transmembrane Helix M2 with Cytoplasmic Domains and Luminal Gating2016

    • Author(s)
      Stefania Danko、山崎 和生、大保 貴嗣、鈴木 裕
    • 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
    • Year and Date
      2016-12-19
    • Related Report
      2016 Annual Research Report
  • [Presentation] Caポンプの素過程構造-機能連関:部位特異的変異、速度論、および中間体・遷移状 態捕捉による解析2016

    • Author(s)
      鈴木 裕、大保 貴嗣、山崎 和生、Stefania Danko
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台
    • Year and Date
      2016-09-25
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 筋小胞体Ca2+ポンプM2ヘリックスの膜貫通部分と細胞質部分の連結領域:エネルギー共役における役割2016

    • Author(s)
      大保 貴嗣、山崎 和生、Stefania Danko、鈴木 裕
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台
    • Year and Date
      2016-09-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] ナノディスクに組み込んだ標品を用いた筋小胞体Ca2+-ATPaseのEP転換ステップに及ぼす脂質組成及びA23187の影響の解析2016

    • Author(s)
      山崎 和生、大保 貴嗣、Stefania Danko、鈴木 裕
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台
    • Year and Date
      2016-09-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] 筋小胞体Ca2+ポンプのエネルギー共役におけるM2ヘリックス膜貫通部分(M2m)と細胞質部分(M2cyt)の連結領域の役割2015

    • Author(s)
      大保貴嗣、山崎和生、Danko Stefania 、鈴木裕
    • Organizer
      日本生体エネルギー研究会 第41回討論会
    • Place of Presentation
      東京
    • Year and Date
      2015-12-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] ナノディスクへ組み込んだ筋小胞体カルシウムポンプを用いたタンパク質―脂質相互作用の解析2015

    • Author(s)
      山崎和生、大保貴嗣、Danko Stefania 、鈴木裕
    • Organizer
      日本生体エネルギー研究会 第41回討論会
    • Place of Presentation
      東京
    • Year and Date
      2015-12-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] 筋小胞体Ca2+ポンプのエネルギー共役におけるM2ヘリックス膜貫通部分(M2m)と細胞質部分(M2cyt)の連結領域の役割2015

    • Author(s)
      大保貴嗣、山崎和生、Danko Stefania 、鈴木裕
    • Organizer
      日本生化学会 第88回大会
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] 筋小胞体Ca2+-ATPaseのEP転換ステップにおけるTyr122-Hydorophobic clusterの集合過程とエネルギー共役2015

    • Author(s)
      山崎和生、大保貴嗣、Danko Stefania 、鈴木裕
    • Organizer
      日本生化学会 第88回大会
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] Long-range Coupling between Catalytic and Transport Sites via Second Transmembrane Helix (M2) in Ca2+-ATPase2015

    • Author(s)
      大保貴嗣、山崎和生、Danko Stefania 、鈴木裕
    • Organizer
      日本生物物理学会 第53回年会
    • Place of Presentation
      金沢
    • Year and Date
      2015-09-13
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Book] P-Type ATPases2015

    • Author(s)
      Hiroshi Suzuki
    • Total Pages
      544
    • Publisher
      Humana Press, Springer
    • Related Report
      2015 Annual Research Report
  • [Book] P-Type ATPases2015

    • Author(s)
      Stefania J. Danko and Hiroshi Suzuki
    • Total Pages
      544
    • Publisher
      Humana Press, Springer
    • Related Report
      2015 Annual Research Report
  • [Funded Workshop] The 15th International ATPase Conference on “Na,K-ATPase and Related Transport ATPases”2017

    • Related Report
      2017 Annual Research Report

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Published: 2015-04-16   Modified: 2020-03-30  

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