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A mechanism regulating the copper acquisition by intracellular proteins

Research Project

Project/Area Number 25291028
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Functional biochemistry
Research InstitutionKeio University

Principal Investigator

FURUKAWA YOSHIAKI  慶應義塾大学, 理工学部, 准教授 (40415287)

Co-Investigator(Renkei-kenkyūsha) NOMURA Takao  慶應義塾大学, 理工学部, 助教 (90597840)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2015: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2014: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2013: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Keywords銅シャペロン / 神経変性疾患 / タンパク質フォールディング / SOD1 / タンパク質凝集 / 筋萎縮性側索硬化症 / 金属タンパク質 / タンパク質 / 銅イオン / 金属シャペロン / ジスルフィド結合
Outline of Final Research Achievements

Copper ion is essential to various physiologies. Most of the copper ions in our bodies exist as the protein-bound form and function as active sites for enzymatic reactions. Also, the level of copper ions in our bodies is strictly controlled, and even slight deviation of the copper ions in physiological conditions will lead to pathological conditions and sometimes fatal diseases. Here, we investigated the mechanism regulating the acquisition of copper ions by intracellular proteins and also examined the molecular pathomechanism of the disease caused by the mis-regulation of copper metabolism in the cell. More precisely, we have noted the activation mechanism of Cu,Zn-superoxide dismutase (SOD1), which requires a copper ion for its enzymatic activity. Also, conformational changes of SOD1 upon dissociation of metal ions have been examined and discussed in relation to the pathogenesis of amyotrophic lateral sclerosis.

Report

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

    (34 results)

All 2016 2015 2014 2013 Other

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Open Access: 5 results,  Acknowledgement Compliant: 5 results) Presentation (22 results) (of which Int'l Joint Research: 2 results,  Invited: 5 results) Remarks (3 results)

  • [Journal Article] A molecular mechanism realizing sequence-specific recognition of nucleic acids by TDP-432016

    • Author(s)
      Yoshiaki Furukawa, Yoh Suzuki, Mami Fukuoka, Kenichi Nagasawa, Kenta Nakagome, Hideaki Shimizu, Atsushi Mukaiyama, and Shuji Akiyama
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 20576-20576

    • DOI

      10.1038/srep20576

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Conformational Disorder of the Most Immature Cu,Zn-Superoxide Dismutase Leading to Amyotrophic Lateral Sclerosis2016

    • Author(s)
      Yoshiaki Furukawa, Itsuki Anzai, Shuji Akiyama, Mizue Imai, Fatima Joy Consul Cruz, Tomohide Saio, Kenichi Nagasawa, Takao Nomura, and Koichiro Ishimori
    • Journal Title

      The Journal of Biological Chemistry

      Volume: 291 Issue: 8 Pages: 4144-4155

    • DOI

      10.1074/jbc.m115.683763

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Aggregation of FET Proteins as a Pathological Change in Amyotrophic Lateral Sclerosis2016

    • Author(s)
      Yoshiaki Furukawa and Eiichi Tokuda
    • Journal Title

      Protein Reviews

      Volume: 印刷中

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Cysteine residues in Cu,Zn-superoxide dismutase are essential to toxicity in Caenorhabditis elegans model of amyotrophic lateral sclerosis2015

    • Author(s)
      Mariko Ogawa, Hisashi Shidara, Kotaro Oka, Masaru Kurosawa, Nobuyuki Nukina, and Yoshiaki Furukawa
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 463 Issue: 4 Pages: 1196-1202

    • DOI

      10.1016/j.bbrc.2015.06.084

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] A primary role for disulfide formation in the productive folding of prokaryotic Cu,Zn-superoxide dismutase2014

    • Author(s)
      Yasuyuki Sakurai, Itsuki Anzai, and Yoshiaki Furukawa
    • Journal Title

      The Journal of Biological Chemistry

      Volume: 289 Issue: 29 Pages: 20139-20149

    • DOI

      10.1074/jbc.m114.567677

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Intranuclear aggregation of mutant FUS/TLS as a molecular pathomechanism of amyotrophic lateral sclerosis2014

    • Author(s)
      Nomura, T., Watanabe, S., Kaneko, K., Yamanaka, K., Nukina, N. & Furukawa, Y.
    • Journal Title

      J. Biol. Chem.

      Volume: 289 Issue: 2 Pages: 1192-1202

    • DOI

      10.1074/jbc.m113.516492

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A seeded propagation of Cu,Zn-superoxide dismutase aggregates in amyotrophic lateral sclerosis2014

    • Author(s)
      Mariko Ogawa and Yoshiaki Furukawa
    • Journal Title

      Frontiers in Cellular Neuroscience

      Volume: 8 Pages: 1-5

    • DOI

      10.3389/fncel.2014.00083

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Redox environment is an intracellular factor to operate distinct pathways for aggregation of Cu,Zn-superoxide dismutase in amyotrophic lateral sclerosis2013

    • Author(s)
      Yoshiaki Furukawa
    • Journal Title

      Frontiers in Cellular Neuroscience

      Volume: 7 Pages: 1-9

    • DOI

      10.3389/fncel.2013.00240

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intracellular seeded aggregation of mutant Cu,Zn-superoxide dismutase associated with amyotrophic lateral sclerosis2013

    • Author(s)
      Furukawa, Y., Kaneko, K., Watanabe, S., Yamanaka, K. & Nukina, N.
    • Journal Title

      FEBS Lett.

      Volume: 587 Issue: 16 Pages: 2500-2505

    • DOI

      10.1016/j.febslet.2013.06.046

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 抗酸化酵素の活性発現を可能にする金属イオンの新たな獲得メカニズム2016

    • Author(s)
      小久保 鉄平、櫻井 靖之、古川 良明
    • Organizer
      日本化学会第96春季年会
    • Place of Presentation
      同志社大学(京都府・京田辺市)
    • Year and Date
      2016-03-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] 細胞内銅イオン輸送を可能にする銅シャペロンのドメイン構造2016

    • Author(s)
      福岡 真実、長野 功、古川 良明
    • Organizer
      日本化学会第96春季年会
    • Place of Presentation
      同志社大学(京都府・京田辺市)
    • Year and Date
      2016-03-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] Lost in metallation: the disaster on a protein structure leading to neurodegeneration2015

    • Author(s)
      Yoshiaki Furukawa, Itsuki Anzai, Kennichi Nagasawa, Shuji Akiyama, Mizue Imai, and Koichiro Ishimori
    • Organizer
      2015 International Chemical Congress of Pacific Basin Societies
    • Place of Presentation
      Honolulu(USA)
    • Year and Date
      2015-12-15
    • Related Report
      2015 Annual Research Report
  • [Presentation] A new mechanism of SOD1 activation regulated by copper chaperone in Clonorchis sinensis2015

    • Author(s)
      Mami Fukuoka, Isao Nagano, and Yoshiaki Furukawa
    • Organizer
      日本生物物理学会第53回年会
    • Place of Presentation
      金沢大学(石川県・金沢市)
    • Year and Date
      2015-09-13
    • Related Report
      2015 Annual Research Report
  • [Presentation] A new intramolecular route to acquire metal ions in superoxide dismutase2015

    • Author(s)
      Teppei Kokubo, Yasuyuki Sakurai, and Yoshiaki Furukawa
    • Organizer
      日本生物物理学会第53回年会
    • Place of Presentation
      金沢大学(石川県・金沢市)
    • Year and Date
      2015-09-13
    • Related Report
      2015 Annual Research Report
  • [Presentation] 銅・亜鉛スーパーオキシドディスムターゼの光と影:抗酸化機能と神経変性疾患2015

    • Author(s)
      古川 良明
    • Organizer
      第28回生物無機化学夏季セミナー
    • Place of Presentation
      伊豆山喜旅館(静岡県・伊東市)
    • Year and Date
      2015-08-28
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Lights and shadows of Cu,Zn-superoxide dismutase2015

    • Author(s)
      Yoshiaki Furukawa
    • Organizer
      The 17th International Conference on Biological Inorganic Chemistry
    • Place of Presentation
      Beijing(China)
    • Year and Date
      2015-07-20
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Fungal isolates with different pathotypes show distinct levels of SOD1 activity controlled by copper chaperone2015

    • Author(s)
      Carolyn Lim, Yoshiyuki Usami, and Yoshiaki Furukawa
    • Organizer
      The 17th International Conference on Biological Inorganic Chemistry
    • Place of Presentation
      Beijing(China)
    • Year and Date
      2015-07-20
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A new maturation mechanism of metalloproteins regulated by formation of a disulfide bond2014

    • Author(s)
      Yoshiaki Furukawa
    • Organizer
      Mini Symposium in IMS
    • Place of Presentation
      分子科学研究所(愛知県・岡崎市)
    • Year and Date
      2014-12-17
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Disulfide formation acts as a redox sensor for enzymatic activation of Cu,Zn-superoxide dismutase2014

    • Author(s)
      Yoshiaki Furukawa
    • Organizer
      7th Asian Biological Inorganic Chemistry Conference
    • Place of Presentation
      Gold Coast (Australia)
    • Year and Date
      2014-11-30 – 2014-12-05
    • Related Report
      2014 Annual Research Report
  • [Presentation] Molecular recognition in copper chaperone system is regulated by Zn ion2014

    • Author(s)
      Yuma Wakahara and Yoshiaki Furukawa
    • Organizer
      7th Asian Biological Inorganic Chemistry Conference
    • Place of Presentation
      Gold Coast (Australia)
    • Year and Date
      2014-11-30 – 2014-12-05
    • Related Report
      2014 Annual Research Report
  • [Presentation] A molecular mechanism of bacterial superoxide dismutase regulated by disulfide formation2014

    • Author(s)
      Yoshiaki Furukawa
    • Organizer
      The 7th Korea-Japan Seminars on Biomolecular Sciences: Experiments and Simulations
    • Place of Presentation
      Seoul (South Korea)
    • Year and Date
      2014-11-26 – 2014-11-28
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] タンパク質ジスルフィドの異常が神経変性疾患の発症に果たす役割:線虫を用いた表現型解析2014

    • Author(s)
      小川 まり子、設樂 久志、岡 浩太郎、古川 良明
    • Organizer
      日本生物物理学会第52回年会
    • Place of Presentation
      札幌コンベンションセンター(北海道・札幌市)
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] ジスルフィド結合のシャッフリングを標的とした異常なタンパク質オリゴマー化の抑制手法2014

    • Author(s)
      安齋 樹、東一 圭祐、向山 厚、秋山 修志、古川 良明
    • Organizer
      日本生物物理学会第52回年会
    • Place of Presentation
      札幌コンベンションセンター(北海道・札幌市)
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] An activation mechanism of human Cu,Zn-superoxide dismutase by its copper chaperone, CCS2014

    • Author(s)
      Carolyn Lim and Yoshiaki Furukawa
    • Organizer
      日本生物物理学会第52回年会
    • Place of Presentation
      札幌コンベンションセンター(北海道・札幌市)
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] ジスルフィド結合が制御するSOD1タンパク質の凝集メカニズム2014

    • Author(s)
      古川 良明
    • Organizer
      2014 タウ研究ミーティング
    • Place of Presentation
      同志社大学東京オフィス(東京都)
    • Year and Date
      2014-08-01
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] タンパク質の凝集に関わる実験的諸問題について2014

    • Author(s)
      古川 良明
    • Organizer
      第14回日本蛋白質科学会年会
    • Place of Presentation
      ワークピア横浜(神奈川県・横浜市)
    • Year and Date
      2014-06-25 – 2014-06-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] 亜鉛イオンが制御する細胞内銅イオン輸送のメカニズム2014

    • Author(s)
      若原 裕磨、本田 一起、古川 良明
    • Organizer
      日本化学会第94春季年会
    • Place of Presentation
      名古屋大学東山キャンパス
    • Related Report
      2013 Annual Research Report
  • [Presentation] ジスルフィド結合による銅・亜鉛スーパーオキサイドディスムターゼ活性の制御メカニズム2014

    • Author(s)
      櫻井 靖之、古川 良明
    • Organizer
      日本化学会第94春季年会
    • Place of Presentation
      名古屋大学東山キャンパス
    • Related Report
      2013 Annual Research Report
  • [Presentation] SOD1への細胞内銅イオン輸送を制御するタンパク質ネットワーク2013

    • Author(s)
      中込 健太、三冨 康司、古川 良明
    • Organizer
      日本生物物理学会第51回年会
    • Place of Presentation
      国立京都国際会館
    • Related Report
      2013 Annual Research Report
  • [Presentation] Molecular recognition of SOD1 by its copper chaperone protein CCS: interplay of zinc ion and disulfide bond controls intracellular copper transport2013

    • Author(s)
      Yoshiaki Furukawa, Kazuki Honda, and Yuma Wakahara
    • Organizer
      16th International Conference on Biological Inorganic Chemistry
    • Place of Presentation
      Grenoble, France
    • Related Report
      2013 Annual Research Report
  • [Presentation] The Activation Mechanism of Bacterial Cu,Zn-Superoxide Dismutase2013

    • Author(s)
      Yasuyuki Sakurai and Yoshiaki Furukawa
    • Organizer
      16th International Conference on Biological Inorganic Chemistry
    • Place of Presentation
      Grenoble, France
    • Related Report
      2013 Annual Research Report
  • [Remarks] Furukawa Lab. Home

    • URL

      http://www.chem.keio.ac.jp/~furukawa/index.html

    • Related Report
      2015 Annual Research Report
  • [Remarks] Furukawa Lab.

    • URL

      http://www.chem.keio.ac.jp/~furukawa/index.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] Furukawa Lab.

    • URL

      http://www.chem.keio.ac.jp/~furukawa/index.html

    • Related Report
      2013 Annual Research Report

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

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