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Functional programming of membrane-bound receptors by On-cell Coordination Chemistry

Research Project

Project/Area Number 15H06318
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field Bio-related chemistry
Research InstitutionKyoto University

Principal Investigator

Kubota Ryou  京都大学, 工学研究科, 助教 (00753146)

Project Period (FY) 2015-08-28 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords金属錯体 / 化学遺伝学 / GPCR / リガンド作動性イオンチャネル / 遺伝子工学 / 膜タンパク質受容体 / 部位特異的変異導入 / Gタンパク質共役受容体 / グルタミン酸受容体 / アドレナリン受容体 / 超分子化学 / 蛋白質 / シグナル伝達 / 分子認識 / 細胞・組織 / 配位結合 / ケミカルバイオロジー
Outline of Final Research Achievements

Membrane-bound receptors in living cells mediate signal transductions by receiving extracellular signals. Despite their biological importance, it is still quite difficult to unveil their functions due to their similar and complicated three-dimensional structures and activation mechanisms. Here we have developed novel chemogenetic approaches, called On-cell Coordination Chemistry (OcCC) in order to artificially control the functions of membrane-bound receptors. We successfully demonstrated that OcCC enabled to control the activities of two types of neurotransmitter receptors, ionchannel type and GPCR type glutamate receptors, in live neurons. Also, we achieved the artificial activation of class A GPCRs by coordination anchor method.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • Research Products

    (13 results)

All 2017 2016 2015

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results) Presentation (12 results) (of which Int'l Joint Research: 3 results,  Invited: 3 results)

  • [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] Metallo-chemical genetics (2) : Selective activation of adrenoceptors by metal complex-agonist conjugates2017

    • Author(s)
      Ryou Kubota, Wataru Nomura, Itaru Hamachi
    • Organizer
      日本化学会第97春季年会
    • Place of Presentation
      慶應義塾大学 (神奈川県横浜市)
    • Year and Date
      2017-03-16
    • Related Report
      2016 Annual Research Report
  • [Presentation] 配位-chemical genetics (3) : 金属錯体-アゴニスト複合体によるアセチルコリン受容体の活性制御2017

    • Author(s)
      岩阪 拓馬、野村 航、窪田 亮、浜地 格
    • Organizer
      日本化学会第97春季年会
    • Place of Presentation
      慶應義塾大学 (神奈川県横浜市)
    • Year and Date
      2017-03-16
    • Related Report
      2016 Annual Research Report
  • [Presentation] Designer Coordination Chemistry Enables Precise Control of Multi-component Self-assembly and Protein Functions2016

    • Author(s)
      Ryou Kubota
    • Organizer
      AsCA2016
    • Place of Presentation
      Hanoi University of Science and Technology, Hanoi, Viet Nam
    • Year and Date
      2016-12-04
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] A Coordination Chemogenetic Approach for Selective Activation of Neurotransmitter Receptors in Living Cells2016

    • Author(s)
      Ryou Kubota, Itaru Hamachi
    • Organizer
      ACBC2016
    • Place of Presentation
      85 Sky Tower Hotel, Kaohsiung, TAIWAN
    • Year and Date
      2016-11-28
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 金属錯体化学による神経伝達物質受容体の人工制御2016

    • Author(s)
      窪田 亮
    • Organizer
      細胞を創る」研究会 9.0
    • Place of Presentation
      早稲田大学 (東京都新宿区)
    • Year and Date
      2016-11-21
    • Related Report
      2016 Annual Research Report
  • [Presentation] グルタミン酸受容体の人工的な活性化における金属錯体選択性2016

    • Author(s)
      小島 憲人、道端 友紀子、窪田 亮、清中 茂樹、浜地 格
    • Organizer
      第10回バイオ関連化学シンポジウム
    • Place of Presentation
      石川県立音楽堂 (石川県金沢市)
    • Year and Date
      2016-09-07
    • Related Report
      2016 Annual Research Report
  • [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
    • Place of Presentation
      石川県立音楽堂 (石川県金沢市)
    • Year and Date
      2016-09-07
    • Related Report
      2016 Annual Research Report
  • [Presentation] 細胞表層配位化学による膜受容体の人工活性化2016

    • Author(s)
      窪田 亮、清中 茂樹、浜地 格
    • Organizer
      生体機能関連化学部会若手の会第28回サマースクール
    • Place of Presentation
      西浦温泉ホテル たつき (愛知県蒲郡市)
    • Year and Date
      2016-07-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] Membrane Receptor Engineering by On-Cell Coordination Chemistry(1):Mechanistic Study on Allosteric Activation of Ionotropic Glutamate Receptors2016

    • Author(s)
      Ryou Kubota, Shigeki Kiyonaka, Itaru Hamachi
    • Organizer
      日本化学会第96春季年会
    • Place of Presentation
      同志社大学・京田辺キャンパス (京都府京田辺市)
    • Year and Date
      2016-03-24
    • Related Report
      2015 Annual Research Report
  • [Presentation] On-cell Coordination Chemistry (OcCC)によるグルタミン酸受容体の選択的活性化2015

    • Author(s)
      窪田 亮、清中 茂樹、浜地 格
    • Organizer
      第9回バイオ関連化学シンポジウム
    • Place of Presentation
      熊本大学・黒髪南地区キャンパス (熊本県熊本市)
    • Year and Date
      2015-09-10
    • Related Report
      2015 Annual Research Report
  • [Presentation] 細胞表層配位化学(OcCC)によるGタンパク質共役受容体のアロステリック活性化2015

    • Author(s)
      野村 航、道籏 友紀子、窪田 亮、清中 茂樹、浜地 格
    • Organizer
      第9回バイオ関連化学シンポジウム
    • Place of Presentation
      熊本大学・黒髪南地区キャンパス (熊本県熊本市)
    • Year and Date
      2015-09-10
    • Related Report
      2015 Annual Research Report
  • [Presentation] Allosteric Activation of Glutamate Receptors by On-cell Coordination Chemistry (OcCC)2015

    • Author(s)
      Ryou Kubota
    • Organizer
      The 5th International Kyoto Symposium on Organic Nanostructures and Molecular Technology
    • Place of Presentation
      Kyoto University Katsura Lounge (京都府京都市)
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited

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Published: 2015-08-26   Modified: 2018-03-22  

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