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Development of novel methods for allosteric activation of receptor subtypes on cell surface

Research Project

Project/Area Number 16H03290
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Chemical biology
Research InstitutionKyoto University

Principal Investigator

Kiyonaka Shigeki  京都大学, 工学研究科, 准教授 (90422980)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Fiscal Year 2018: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2016: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Keywordsグルタミン酸受容体 / ケミカルバイオロジー / アロステリック活性化 / サブタイプ / 細胞膜受容体
Outline of Final Research Achievements

Development of new techniques for artificial regulation of specific cells in our body is one of essential technologies in life science researches. We have recently reported a new method for artifical activation of ion-channel-type glutamate receptors using coordination chemistry in live cells. In this method, two histidine mutations were introduced near the ligand-binding domain. Addition of Pd(bpy) complex, which coordinates to the histidine residues in a bidentate fashion, lead to stabilize the active conformation of the receptors for allosteric activation. Here, we successfully expanded our method for artificial regulation of G-protein coupled receptors (GPCRs). This means that our method is useful for artificial regulation of many kinds of receptors in live cells.

Academic Significance and Societal Importance of the Research Achievements

本研究では、我々の開発した受容体の人為的な活性化法が、イオンチャネル型受容体だけでなくGタンパク質共役型受容体も含めた幅広いタンパク質に対して拡張できる可能性を示した。また、この手法が神経細胞においても適用できることも確認した。この結果は、我々の方法論が、脳などの複雑な生体組織において狙った細胞の標的受容体を人為的に活性制御してその機能解明を行えるという、新たな方法論になり得ることを示唆する。

Report

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

    (13 results)

All 2019 2018 2017 2016

All Journal Article (4 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 4 results,  Open Access: 2 results) Presentation (9 results) (of which Int'l Joint Research: 3 results,  Invited: 4 results)

  • [Journal Article] Construction of ligand assay systems by protein-based semisynthetic biosensors2019

    • Author(s)
      Sakamoto Seiji、Kiyonaka Shigeki、Hamachi Itaru
    • Journal Title

      Current Opinion in Chemical Biology

      Volume: 50 Pages: 10-18

    • DOI

      10.1016/j.cbpa.2019.02.011

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chemogenetic Approach Using Ni(II) Complex?Agonist Conjugates Allows Selective Activation of Class A G-Protein-Coupled Receptors2018

    • Author(s)
      Kubota Ryou、Nomura Wataru、Iwasaka Takuma、Ojima Kento、Kiyonaka Shigeki、Hamachi Itaru
    • Journal Title

      ACS Central Science

      Volume: 4 Issue: 9 Pages: 1211-1221

    • DOI

      10.1021/acscentsci.8b00390

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Chemical labelling for visualizing native AMPA receptors in live neurons.2017

    • Author(s)
      Wakayama, S., Kiyonaka, S., Arai, I., Kakegawa, W., Matsuda, S., Ibata, K., Nemoto, Y.L., Kusumi, A., Yuzaki, M., Hamachi, I.
    • Journal Title

      Nature Communications

      Volume: 8 Issue: 1 Pages: 14850-14850

    • DOI

      10.1038/ncomms14850

    • NAID

      120006600363

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Allosteric activation of membrane-bound glutamate receptors using coordination chemistry within living cells2016

    • Author(s)
      Shigeki Kiyonaka, Ryou Kubota, Yukiko Michibata, Masayoshi Sakakura, Hideo Takahashi, Tomohiro Numata, Ryuji Inoue, Michisuke Yuzaki, Itaru Hamachi
    • Journal Title

      Nat. Chem.

      Volume: 8 Issue: 10 Pages: 958-967

    • DOI

      10.1038/nchem.2554

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Coordination chemogenetics for allosteric activation of endogenous GPCR-type glutamate receptors2019

    • Author(s)
      Kento Ojima, Wataru Kakegawa, Yukiko Michibata, Ryou Kubota, Michisuke Yuzaki, Shigeki Kiyonaka, Itaru Hamachi
    • Organizer
      日本化学会第99春季年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 新たな GPCR 活性制御法:配位ケモジェネティクス2019

    • Author(s)
      清中 茂樹
    • Organizer
      第48回日本心脈管作動物質学会 (富山国際会議場)
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 配位ケモジェネティクスによるグルタミン酸受容体サブタイプ特異的な活性制御2019

    • Author(s)
      清中 茂樹
    • Organizer
      第16回レドックス・ライフイノベーションシンポジウム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Chemogenetic Approach for Allosteric Activation of Neurotransmitter Receptors on Living Cells2017

    • Author(s)
      Shigeki Kiyonaka
    • Organizer
      High Throughput Chemistry & Chemical Biology, Gordon Research Conference
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Novel chemical-biological technologies for elucidating physiological roles of neurotransmitter receptors2017

    • Author(s)
      Shigeki Kiyonaka
    • Organizer
      第60回日本神経化学大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Coordination chemical genetics of receptors for artificially regulating minority events2017

    • Author(s)
      Shigeki Kiyonaka
    • Organizer
      第55回日本生物物理学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Novel Chemical Approach for Allosteric Activation of Glutamate Receptors on Live Cells2016

    • Author(s)
      Shigeki Kiyonaka
    • Organizer
      第21回 iCeMS国際シンポジウム
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] グルタミン酸受容体の選択的活性化を可能とする錯体化学的アプローチ2016

    • Author(s)
      窪田 亮、道籏 友紀子、清中 茂樹、浜地 格
    • Organizer
      第10回バイオ関連化学シンポジウム
    • Related Report
      2016 Annual Research Report
  • [Presentation] Visualization of native AMPA receptors in live neurons by a novel chemical approach2016

    • Author(s)
      Shigeki Kiyonaka, Sho Wakayama, Itaru Arai, Wataru Kakegawa, Michisuke Yuzaki, Itaru Hamachi
    • Organizer
      The 47th NIPS International Symposium "Decoding Synapses"
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research

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Published: 2016-04-21   Modified: 2020-03-30  

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