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分子夾雑環境におけるタンパク質の金属イオン獲得メカニズム

Publicly Offered Research

Project AreaChemical Approaches for Miscellaneous / Crowding Live Systems
Project/Area Number 18H04564
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Research InstitutionKeio University

Principal Investigator

古川 良明  慶應義塾大学, 理工学部(矢上), 准教授 (40415287)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Discontinued (Fiscal Year 2019)
Budget Amount *help
¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2019: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2018: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywords銅シャペロン / 金属タンパク質
Outline of Annual Research Achievements

生体内において、銅イオンは様々なタンパク質に結合し、酸化還元活性の中心として機能している。一方、遊離状態の銅イオンは、細胞にとって有毒な活性酸素種を生成することが知られている。そのため、細胞内のほぼ全て銅イオンは何らかの生体分子に結合した状態で存在しており、遊離状態の銅イオンは細胞1つあたりわずか1個程度だと言われている。このような生体内環境において、細胞内に取り込まれた銅イオンは、「銅シャペロン」と呼ばれる銅イオン運搬タンパク質に結合することで、銅イオンを必要とする種々のタンパク質へと供給される。代表的な銅イオン結合タンパク質である銅・亜鉛スーパーオキシドディスムターゼ(SOD1)は、銅イオン、亜鉛イオンを結合し、分子内でS-S結合を形成することで活性化する抗酸化酵素である。SOD1は銅シャペロンCCSから銅イオンの供給を受けることが知られている。実際に、CCS遺伝子を欠損させた酵母やマウスにおいて、SOD1の活性が消失、あるいは、著しく減少することが報告されている。また、生体から抽出したSOD1には銅イオンが1対1で結合していることから、生体内の全てのSOD1がCCSから銅イオンを供給されていることが考えられる。例えば、SOD1に対してCCSと銅イオンをどちらも添加した場合、銅イオンのみを添加した場合に比べて、SOD1の活性が劇的に上昇することが報告されている。しかし、試験管内で活性化したSOD1に関して、酵素活性の定性的な評価は多くなされているものの、CCSによる銅イオンの供給を定量的に評価している報告はほとんどなく、実際にSOD1に結合した銅イオンの量は不明瞭となっている。本研究では、銅イオンのキレート剤であるBCSを利用することで、SOD1に結合した銅イオンを簡便に定量できる手法を確立し、CCSによるSOD1への銅イオン供給反応について定量的な評価を試みた。

Research Progress Status

令和元年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和元年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (33 results)

All 2020 2019 2018 Other

All Journal Article (10 results) (of which Peer Reviewed: 9 results,  Open Access: 6 results) Presentation (20 results) (of which Int'l Joint Research: 11 results,  Invited: 7 results) Book (1 results) Remarks (2 results)

  • [Journal Article] Oxidative misfolding of Cu/Zn-superoxide dismutase triggered by non-canonical intramolecular disulfide formation2020

    • Author(s)
      Anzai Itsuki、Tokuda Eiichi、Handa Sumika、Misawa Hidemi、Akiyama Shuji、Furukawa Yoshiaki
    • Journal Title

      Free Radical Biology and Medicine

      Volume: 147 Pages: 187-199

    • DOI

      10.1016/j.freeradbiomed.2019.12.017

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prion-like Properties of Misfolded Cu/Zn-superoxide Dismutase in Amyotrophic Lateral Sclerosis: Update and Perspectives2019

    • Author(s)
      Tokuda Eiichi、Marklund Stefan L.、Furukawa Yoshiaki
    • Journal Title

      YAKUGAKU ZASSHI

      Volume: 139 Issue: 7 Pages: 1015-1019

    • DOI

      10.1248/yakushi.18-00165-5

    • NAID

      130007670812

    • ISSN
      0031-6903, 1347-5231
    • Year and Date
      2019-07-01
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Wild-type Cu/Zn-superoxide dismutase is misfolded in cerebrospinal fluid of sporadic amyotrophic lateral sclerosis2019

    • Author(s)
      Tokuda Eiichi、Takei Yo-ichi、Ohara Shinji、Fujiwara Noriko、Hozumi Isao、Furukawa Yoshiaki
    • Journal Title

      Molecular Neurodegeneration

      Volume: 14 Issue: 1 Pages: 42-42

    • DOI

      10.1186/s13024-019-0341-5

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sequence- and seed-structure-dependent polymorphic fibrils of alpha-synuclein2019

    • Author(s)
      Tanaka Goki、Yamanaka Tomoyuki、Furukawa Yoshiaki、Kajimura Naoko、Mitsuoka Kaoru、Nukina Nobuyuki
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

      Volume: 19 Issue: 6 Pages: 30065-1

    • DOI

      10.1016/j.bbadis.2019.02.013

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Biochemical and morphological classification of disease-associated alpha-synuclein mutants aggregates2019

    • Author(s)
      Tanaka Goki、Yamanaka Tomoyuki、Furukawa Yoshiaki、Kajimura Naoko、Mitsuoka Kaoru、Nukina Nobuyuki
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 508 Issue: 3 Pages: 729-734

    • DOI

      10.1016/j.bbrc.2018.11.200

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pathological roles of copper dynamics in amyotrophic lateral sclerosis2018

    • Author(s)
      古川良明
    • Journal Title

      生化学

      Volume: 90 Issue: 3 Pages: 311-319

    • DOI

      10.14952/SEIKAGAKU.2018.900311

    • ISSN
      0037-1017
    • Year and Date
      2018-06-25
    • Related Report
      2018 Annual Research Report
  • [Journal Article] Rapid dissemination of alpha-synuclein seeds through neural circuits in an in-vivo prion-like seeding experiment2018

    • Author(s)
      Okuzumi Ayami、Kurosawa Masaru、Hatano Taku、Takanashi Masashi、Nojiri Shuuko、Fukuhara Takeshi、Yamanaka Tomoyuki、Miyazaki Haruko、Yoshinaga Saki、Furukawa Yoshiaki、Shimogori Tomomi、Hattori Nobutaka、Nukina Nobuyuki
    • Journal Title

      Acta Neuropathologica Communications

      Volume: 6 Issue: 1 Pages: 96-96

    • DOI

      10.1186/s40478-018-0587-0

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Elimination of TDP-43 inclusions linked to amyotrophic lateral sclerosis by a misfolding-specific intrabody with dual proteolytic signals.2018

    • Author(s)
      Tamaki Y, Shodai A, Morimura T, Hikiami R, Minamiyama S, Ayaki T, Tooyama I, Furukawa Y, Takahashi R, Urushitani M.
    • Journal Title

      Scientific Reports

      Volume: 印刷中 Issue: 1 Pages: 6030-6030

    • DOI

      10.1038/s41598-018-24463-3

    • NAID

      120006482849

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cu/Zn-superoxide dismutase forms fibrillar hydrogels in a pH-dependent manner via a water-rich extended intermediate state2018

    • Author(s)
      Fujiwara Noriko、Wagatsuma Michiru、Oba Naoto、Yoshihara Daisaku、Tokuda Eiichi、Sakiyama Haruhiko、Eguchi Hironobu、Ichihashi Motoko、Furukawa Yoshiaki、Inoue Tadashi、Suzuki Keiichiro
    • Journal Title

      PLOS ONE

      Volume: 13 Issue: 10 Pages: e0205090-e0205090

    • DOI

      10.1371/journal.pone.0205090

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of a novel zinc-binding protein, C1orf123, as an interactor with a heavy metal-associated domain2018

    • Author(s)
      Furukawa Yoshiaki、Lim Carolyn、Tosha Takehiko、Yoshida Koki、Hagai Tomoaki、Akiyama Shuji、Watanabe Shoji、Nakagome Kenta、Shiro Yoshitsugu
    • Journal Title

      PLOS ONE

      Volume: 13 Issue: 9 Pages: e0204355-e0204355

    • DOI

      10.1371/journal.pone.0204355

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 大腸菌におけるスーパーオキシドディスムターゼの銅イオン獲得メカニズム2020

    • Author(s)
      古川 良明
    • Organizer
      日本農芸化学会大会2020
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Demetallated Cu/Zn-superoxide dismutase as a pathogenic entity causing neurodegeneration2019

    • Author(s)
      Yoshiaki Furukawa
    • Organizer
      Towards a cure for amyloid diseases: a successful example of precision and translational medicine
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Misfolded SOD1 as a pathological species in sporadic forms of amyotrophic lateral sclerosis2019

    • Author(s)
      Yoshiaki Furukawa
    • Organizer
      The 4th Joint Conference between KMU and Keio University
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] タンパク質のミスフォールディングがもたらす神経変性疾患2019

    • Author(s)
      古川 良明
    • Organizer
      医工連携シンポジウム
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Demetallated Cu/Zn-superoxide dismutase as a pathogenic entity causing neurodegeneration2019

    • Author(s)
      Yoshiaki Furukawa
    • Organizer
      Biometal Science
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] A misfolding of Cu/Zn-superoxide dismutase in amyotrophic lateral sclerosis2019

    • Author(s)
      Yoshiaki Furukawa
    • Organizer
      The 10th APRU Population Aging Conference
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A misfolding mechanism of Cu/Zn-superoxide dismutase under oxidative conditions of amyotrophic lateral sclerosis2019

    • Author(s)
      Yoshiaki Furukawa, Itsuki Anzai, Eiichi Tokuda, Atsushi Mukaiyama, Shuji Akiyama
    • Organizer
      15th International Symposium on Applied Bioinorganic Chemistry
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 神経変性疾患関連タンパク質SOD1の自己酸化によるミスフォールディング機構2019

    • Author(s)
      安齋 樹、徳田 栄一、向山 厚、秋山 修志、古川 良明
    • Organizer
      第19回日本蛋白質科学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 銅シャペロンCCSがSOD1タンパク質に銅イオンを供給するメカニズム2019

    • Author(s)
      羽飼 友昭、福岡 真実、古川 良明
    • Organizer
      第19回日本蛋白質科学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 大腸菌における銅・亜鉛スーパーオキシドディスムターゼの生理的役割2019

    • Author(s)
      古川 良明、吉田 昴生
    • Organizer
      第19回日本蛋白質科学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] バクテリアにおける銅・亜鉛スーパーオキシドディスムターゼの生理的役割2019

    • Author(s)
      古川 良明、吉田 昂生、草野 孝央、高橋 愛海
    • Organizer
      メタルバイオサイエンス研究会2019
    • Related Report
      2019 Annual Research Report
  • [Presentation] Metal-deficiency in Cu/Zn-superoxide dismutase: a potential cause of motor neuron disease, ALS2018

    • Author(s)
      Yoshiaki Furukawa
    • Organizer
      9th Asian Biological Inorganic Chemistry Conference
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] A misfolding mechanism of Cu/Zn-superoxide dismutase under oxidative conditions of amyotrophic lateral sclerosis2018

    • Author(s)
      Itsuki Anzai, Eiichi Tokuda, Atsushi Mukaiyama, Shuji Akiyama, and Yoshiaki Furukawa
    • Organizer
      9th Asian Biological Inorganic Chemistry Conference
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Factors controlling expression levels of periplasmic Cu/Zn-superoxide dismutase in Escherichia coli2018

    • Author(s)
      Koki Yoshida and Yoshiaki Furukawa
    • Organizer
      9th Asian Biological Inorganic Chemistry Conference
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Conformation-dependent toxicity of Cu/Zn-superoxide dismutase in Caenorhabditis elegans2018

    • Author(s)
      Ayano Toba, Eiichi Tokuda, and Yoshiaki Furukawa
    • Organizer
      9th Asian Biological Inorganic Chemistry Conference
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A network for intracellular copper distribution controlled by interactions between copper chaperones2018

    • Author(s)
      Kyoka Matsumoto, Kenta Nakagome, and Yoshiaki Furukawa
    • Organizer
      9th Asian Biological Inorganic Chemistry Conference
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Wild-type SOD1 is misfolded in cerebrospinal fluid of sporadic ALS2018

    • Author(s)
      Yoshiaki Furukawa, Eiichi Tokuda, Shinji Ohara, Noriko Fujiwara
    • Organizer
      22nd International Symposium on ALS/MND
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 神経変性疾患に見られる生体内銅イオン動態の異常2018

    • Author(s)
      古川良明
    • Organizer
      第6回メタロミクス研究フォーラム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] A mechanism on copper acquisition of bacterial Cu/Zn-superoxide dismutase2018

    • Author(s)
      古川良明
    • Organizer
      第56回日本生物物理学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 筋萎縮性側索硬化症における銅・亜鉛結合タンパク質SOD1のミスフォールディングメカニズム2018

    • Author(s)
      古川良明
    • Organizer
      第18回日本蛋白質科学会年会
    • Related Report
      2018 Annual Research Report
  • [Book] 食と医療 2018 FALL-WINTER Vol.72018

    • Author(s)
      「食と医療」事務局
    • Total Pages
      116
    • Publisher
      講談社
    • ISBN
      9784065140581
    • Related Report
      2018 Annual Research Report
  • [Remarks] Furukawa Lab. Home

    • URL

      https://furukawa-lab.org

    • Related Report
      2019 Annual Research Report
  • [Remarks] 慶應理工のタンパク質科学(生命機構化学・古川研究室)

    • URL

      https://furukawa.mixh.jp

    • Related Report
      2018 Annual Research Report

URL: 

Published: 2018-04-23   Modified: 2021-01-27  

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