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Structural and functional analysis of sodium selective permeation of voltage dependent sodium channel

Research Project

Project/Area Number 17K17795
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Biophysics
General physiology
Research InstitutionNagoya University

Principal Investigator

Irie Katsumasa  名古屋大学, 細胞生理学研究センター, 助教 (20415087)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywordsイオンチャネル / X線結晶構造解析 / イオン選択性 / 電気生理学 / 構造解析 / 構造生理学 / 構造活性相関
Outline of Final Research Achievements

Ion channels are important proteins that play essential roles in nerve signal transmission and muscle contraction. We have clarified the role of amino acids that compose the permeation pathway that determines which the species of ions can permeate the channel. We have succeeded in identifying amino acids that distinguish the size of ions, and single point mutation that increases the selectivity of lithium ions.
In addition, we discovered the novel native bacterial calcium channel for the first time in the world. The channel was found in bacteria relatively close to common ancestors of life. This channel has similarities to the calcium channel in humans and other higher organisms, and it was confirmed that glycine, which is well conserved in ion pathway, is important in permeation of calcium ion.

Academic Significance and Societal Importance of the Research Achievements

これらの成果は神経伝達の電気信号の電線、すなわち思考や記憶の基本素子ともいえるイオンチャネルの信号を伝える方法について明らかにするものであり、イオン選択性の獲得過程であるイオンチャネル進化においてミッシングリンクであった先祖型のカルシウムチャネルについての知見を与えるものです。この結果をもとにした機能理解によって、これらのチャネルが関わる高血圧・不整脈・疼痛などに効果的に作用する薬剤の開発の基礎となることも期待されます。また、産業利用に有用なイオンであるリチウムイオンの透過効率が上がるチャネルはし、選択的な回収方法などのへの技術応用につながる成果になります。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (23 results)

All 2020 2019 2018 2017 Other

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 3 results) Presentation (10 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results) Remarks (6 results)

  • [Journal Article] A native prokaryotic voltage-dependent calcium channel with a novel selectivity filter sequence2020

    • Author(s)
      Shimomura Takushi、Yonekawa Yoshiki、Nagura Hitoshi、Tateyama Michihiro、Fujiyoshi Yoshinori、Irie Katsumasa
    • Journal Title

      eLife

      Volume: 9 Pages: 1-21

    • DOI

      10.7554/elife.52828

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A single K+-binding site in the crystal structure of the gastric proton pump2019

    • Author(s)
      Yamamoto Kenta、Dubey Vikas、Irie Katsumasa、Nakanishi Hanayo、Khandelia Himanshu、Fujiyoshi Yoshinori、Abe Kazuhiro
    • Journal Title

      eLife

      Volume: 8

    • DOI

      10.7554/elife.47701

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Genetic manipulation of autonomic nerve fiber innervation and activity and its effect on breast cancer progression2019

    • Author(s)
      Kamiya Atsunori、Hayama Yohsuke、Kato Shigeki、Shimomura Akihiko、Shimomura Takushi、Irie Katsumasa、Kaneko Ryosuke、Yanagawa Yuchio、Kobayashi Kazuto、Ochiya Takahiro
    • Journal Title

      Nature Neuroscience

      Volume: 22 Issue: 8 Pages: 1289-1305

    • DOI

      10.1038/s41593-019-0430-3

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Morphologic determinant of tight junctions revealed by claudin-3 structures2019

    • Author(s)
      Nakamura Shun、Irie Katsumasa、Tanaka Hiroo、Nishikawa Kouki、Suzuki Hiroshi、Saitoh Yasunori、Tamura Atsushi、Tsukita Sachiko、Fujiyoshi Yoshinori
    • Journal Title

      Nature Communications

      Volume: 10 Issue: 1 Pages: 816-816

    • DOI

      10.1038/s41467-019-08760-7

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Crystal structures of the gastric proton pump2018

    • Author(s)
      Abe Kazuhiro、Irie Katsumasa、Nakanishi Hanayo、Suzuki Hiroshi、Fujiyoshi Yoshinori
    • Journal Title

      Nature

      Volume: 556 Issue: 7700 Pages: 214-218

    • DOI

      10.1038/s41586-018-0003-8

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Enhancement of the thermostability of mouse claudin-3 on complex formation with the carboxyl-terminal region of Clostridium perfringens enterotoxin improves crystal quality2018

    • Author(s)
      Nakamura Shun、Fujiyoshi Yoshinori、Irie Katsumasa
    • Journal Title

      Acta Crystallographica Section F Structural Biology Communications

      Volume: 74 Issue: 3 Pages: 150-155

    • DOI

      10.1107/s2053230x18002005

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Optimized expression and purification of NavAb provide the structural insight into the voltage dependence2018

    • Author(s)
      Irie Katsumasa、Haga Yukari、Shimomura Takushi、Fujiyoshi Yoshinori
    • Journal Title

      FEBS Letters

      Volume: 592 Issue: 2 Pages: 274-283

    • DOI

      10.1002/1873-3468.12955

    • NAID

      120006473551

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] 新しい選択性フィルター配列を有する原核生物由来膜電位感受性カルシウムチャネルの同定と機能解析2019

    • Author(s)
      下村拓史、米川佳樹、名倉仁、立山充博、藤吉好則、〇入江克雅
    • Organizer
      "生理学研究所 研究会 「イオンチャネルと生体膜のダイナミズム: 構造生物学の先にあるもの」"
    • Related Report
      2019 Annual Research Report
  • [Presentation] Tutorial for physiologists:“Practical Approaches to Protein Structural Information”2019

    • Author(s)
      Katsumasa Irie
    • Organizer
      9th FAOPS congress
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Unexpected primary sequence of the selectivity filter of endogenous prokaryotic voltage-gated calcium channel2018

    • Author(s)
      Katsumasa Irie, Takushi Shimomura, Toshiki Yonekawa, Hitoshi Nagura, and Yoshinori Fujiyoshi
    • Organizer
      The 49th NIPS International Symposium
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Asymmetric interaction of permeating cation and local anesthetic with homo-tetrameric sodium channel2018

    • Author(s)
      入江 克雅
    • Organizer
      第56回日本生物物理学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 構造生理学的アプローチによるナトリウムチャネルのイオン透過機構の解析2018

    • Author(s)
      入江 克雅
    • Organizer
      蛋白研セミナー:構造情報に基づいた膜イオン輸送タンパク質の 生理機能の解明に向けて
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 複数の変異体を用いた原核生物由来ナトリウムチャネルの選択性フィルターの構造解析2018

    • Author(s)
      入江克雅、中村駿、藤吉好則
    • Organizer
      第95回日本生理学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 「四量体型ナトリウムチャネルの構造機能研究とその応用」2017

    • Author(s)
      入江克雅
    • Organizer
      第2回 医薬系3部局交流シンポジウム
    • Related Report
      2017 Research-status Report
  • [Presentation] ナトリウムイオン選択的透過機構の解明を目指したNavAb変異体の構造解析2017

    • Author(s)
      入江克雅
    • Organizer
      第2 回 イオンチャネル研究会 ~チャネル七夕~
    • Related Report
      2017 Research-status Report
  • [Presentation] 四量体型ナトリウムチャネルにみられる 透過イオンや阻害剤との 非対称な相互作用2017

    • Author(s)
      入江克雅
    • Organizer
      平成29年度生理学研究所研究会 「膜システムの機能的・構造的統合」
    • Related Report
      2017 Research-status Report
  • [Presentation] Characterization of prokaryotic voltage-gated calcium channel2017

    • Author(s)
      Katsumasa Irie, Takushi Shimomura, Toshiki Yonekawa & Yoshinori Fujiyoshi
    • Organizer
      第55回日本生物物理学会年会
    • Related Report
      2017 Research-status Report
  • [Remarks] 細菌のセンサーから紐解く 神経刺激を伝えるタンパク質の太古の姿

    • URL

      http://www.nagoya-u.ac.jp/about-nu/public-relations/researchinfo/upload_images/20200225_ps1.pdf

    • Related Report
      2019 Annual Research Report
  • [Remarks] Discovery of bacterial calcium channels

    • URL

      http://en.nagoya-u.ac.jp/research/activities/news/2020/02/discovery-of-bacterial-ancestor-yields-new-insight-into-calcium-channels.html

    • Related Report
      2019 Annual Research Report
  • [Remarks] Bacterial ancestor of calcium channels

    • URL

      https://elifesciences.org/for-the-press/ccb788b3/discovery-of-bacterial-ancestor-yields-new-insight-on-calcium-channels

    • Related Report
      2019 Annual Research Report
  • [Remarks] Microbes hint at primeval roots for animal protein

    • URL

      https://www.nature.com/articles/d41586-020-00596-2

    • Related Report
      2019 Annual Research Report
  • [Remarks] 細胞と細胞を張り合わせるジッパーの形の違いを生み出す仕組みの解明

    • URL

      http://www.nagoya-u.ac.jp/about-nu/public-relations/researchinfo/upload_images/20190227_ps.pdf

    • Related Report
      2018 Research-status Report
  • [Remarks] 世界初!胃酸分泌を担う胃プロトンポンプの構造を解明

    • URL

      http://www.nagoya-u.ac.jp/about-nu/public-relations/researchinfo/upload_images/20180405_ps_1.pdf

    • Related Report
      2018 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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