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Reverse structural biology of conformational dynamics and signal transduction mechanisms of taste receptors

Research Project

Project/Area Number 20H03195
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 43020:Structural biochemistry-related
Research InstitutionOkayama University

Principal Investigator

Yamashita Atsuko  岡山大学, 医歯薬学域, 教授 (10321738)

Co-Investigator(Kenkyū-buntansha) 日下部 裕子  国立研究開発法人農業・食品産業技術総合研究機構, 食品研究部門, グループ長補佐 (90353937)
清中 茂樹  名古屋大学, 工学研究科, 教授 (90422980)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2022: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2021: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2020: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Keywords味覚受容体 / 受容体 / 味覚 / 構造解析
Outline of Research at the Start

味覚受容体の細胞外領域は、外界からの多様な化学情報を認識し、その情報を変換して生体内に伝える主な役割を担う。各種リガンドは、細胞外領域が取りうる多様なコンフォメーション間の遷移を引き起こすことで、シグナル伝達の程度を決定すると考えられる。一方、これまで各コンフォメーションの高分解能構造情報と構造動態・シグナル伝達状態との紐付けが明確にできておらず、情報変換メカニズムの理解が途上にあった。そこで、受容体が取るコンフォメーションの特定の状態をそれぞれ戦略的に捕捉し、その高分解能構造とシグナル伝達状態を明らかにする「逆構造生物学」的アプローチから、受容体による化学情報変換メカニズムの解明を目指す。

Outline of Final Research Achievements

Structural and functional analyses of sweet and umami taste receptors (T1rs) were performed using the ligand-binding domain (LBD) of medaka T1r2a/T1r3, the current sole protein amenable for structural analysis, as a model T1r protein. We first identified ligands that exhibit binding to LBD and elicit its conformational change similarly to other T1r agonists but evoke no noticeable responses of the receptor. We also found that chloride ions, whose actions on T1rs have not been explored, exhibit binding to LBD and elicit its conformational change as similar as other agonists and evoke a preferable taste sensation via T1rs.

Academic Significance and Societal Importance of the Research Achievements

甘味受容体・うま味受容体T1rについては、これまでに得られている構造情報が極めて限定的であった。本研究課題で、受容体への作用の異なるリガンドの結合状態構造を明らかにしたことで、今後T1r活性化機構を明らかにしていく上での基盤情報を得た。さらに、本研究課題において、塩化物イオンのT1rへの作用を新たに解明した。この作用部位は、解析に用いたメダカ受容体のみならず、ヒトも含めた他のT1rにも共通して保存されていると考えられることから、食品産業に重要な甘味・うま味受容の理解に新たな知見を提供したことに加え、適量の摂取が健康維持に重要な食塩の味覚感知に対しても、新たな観点を提供した。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (30 results)

All 2023 2022 2021 2020 Other

All Int'l Joint Research (5 results) Journal Article (9 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 7 results,  Open Access: 5 results) Presentation (13 results) (of which Int'l Joint Research: 3 results,  Invited: 6 results) Book (2 results) Remarks (1 results)

  • [Int'l Joint Research] Max Planck Institute(ドイツ)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] Monell Chemical Senses Center(米国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] University of Nantes(フランス)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] Max Planck Institute(ドイツ)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Max Planck Institute for Ornithology(ドイツ)

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Development of Hidden Markov Modeling of Molecular Orientations and Structures from High-Speed Atomic Force Microscopy Time-Series Images2023

    • Author(s)
      Tomonori Ogane, Daisuke Noshiro, Toshio Ando, Atsuko Yamashita, Yuji Sugita, Yasuhiro Matsunaga
    • Journal Title

      PLoS Comp. Biol.

      Volume: 18 Issue: 12 Pages: e1010384-e1010384

    • DOI

      10.1371/journal.pcbi.1010384

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chloride ions evoke taste sensations by binding to the extracellular ligand-binding domain of sweet/umami taste receptors2023

    • Author(s)
      Atsumi N, Yasumatsu K, Takashina Y, Ito C, Yasui N, Margolskee RF, Yamashita A
    • Journal Title

      eLife

      Volume: 12

    • DOI

      10.7554/elife.84291

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Structure and mechanism of oxalate transporter OxlT in an oxalate-degrading bacterium in the gut microbiota2023

    • Author(s)
      Jaunet-Lahary Titouan、Shimamura Tatsuro、Hayashi Masahiro、Nomura Norimichi、Hirasawa Kouta、Shimizu Tetsuya、Yamashita Masao、Tsutsumi Naotaka、Suehiro Yuta、Kojima Keiichi、Sudo Yuki、Tamura Takashi、Iwanari Hiroko、Hamakubo Takao、Iwata So、Okazaki Kei-ichi、Hirai Teruhisa、Yamashita Atsuko
    • Journal Title

      Nature Communications

      Volume: 14 Issue: 1 Pages: 1730-1730

    • DOI

      10.1038/s41467-023-36883-5

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] T1R2-mediated sweet sensing in a lizard2022

    • Author(s)
      Liang Qiaoyi、Ko Meng-Ching、Ng Nathaniel S.R.、Reh Borja、Lee Jessica G.H.、Yamashita Atsuko、Nishihara Hidenori、Toda Yasuka、Baldwin Maude W.
    • Journal Title

      Current Biology

      Volume: 32 Issue: 23 Pages: R1302-R1303

    • DOI

      10.1016/j.cub.2022.10.061

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Coordination chemogenetics for activation of GPCR-type glutamate receptors in brain tissue2022

    • Author(s)
      Ojima Kento、Kakegawa Wataru、Yamasaki Tokiwa、Miura Yuta、Itoh Masayuki、Michibata Yukiko、Kubota Ryou、Doura Tomohiro、Miura Eriko、Nonaka Hiroshi、Mizuno Seiya、Takahashi Satoru、Yuzaki Michisuke、Hamachi Itaru、Kiyonaka Shigeki
    • Journal Title

      Nature Communications

      Volume: 13 Issue: 1 Pages: 1-17

    • DOI

      10.1038/s41467-022-30828-0

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 味覚受容体の構造と働き2021

    • Author(s)
      山下敦子
    • Journal Title

      milsil

      Volume: 14 Pages: 6-8

    • Related Report
      2021 Annual Research Report
  • [Journal Article] A sweet protein monellin as a non-antibody scaffold for synthetic binding proteins2021

    • Author(s)
      Yasui N, Nakamura K, Yamashita A
    • Journal Title

      J. Biochem.

      Volume: 169 Issue: 5 Pages: 585-599

    • DOI

      10.1093/jb/mvaa147

    • NAID

      120007182873

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 受容体タンパク質を用いた味覚感知初反応の解析と応用2021

    • Author(s)
      山下敦子, 芦川雄二, 南後恵理子, 安井典久
    • Journal Title

      バイオサイエンスとインダストリー

      Volume: 79 Pages: 86-89

    • NAID

      40022533057

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Current pivotal strategies leading a difficult target protein to a sample suitable for crystallographic analysis2020

    • Author(s)
      Yamashita A
    • Journal Title

      Biochem. Soc. Trans.

      Volume: 48 Issue: 4 Pages: 1661-1673

    • DOI

      10.1042/bst20200106

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Presentation] Chloride ion-binding to the extracellular ligand-binding domain of sweet/umami taste receptors evokes taste sensation2023

    • Author(s)
      Atsuko Yamashita, Nanako Atsumi, Keiko Yasumatsu, Yuriko Takashina, Chiaki Ito, Norihisa Yasui, Robert F. Margolskee
    • Organizer
      The 19th International Symposium on Molecular and Neural Mechanisms of Taste and Olfactory Perception
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] メダカ由来味覚受容体T1R2a/T1R3細胞外領域のリガンド結合解析2022

    • Author(s)
      石田 光,安井 典久,山下 敦子
    • Organizer
      日本味と匂学会第56回大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] メダカ由来味覚受容体T1R2a/T1R3リガンド結合領域に対する疎_性アミノ酸の作_解析および結合構造解析2022

    • Author(s)
      新田純矢、安井典久、堤尚孝、山下敦子
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 受容体組換え発現タンパク質を用いたリガンド結合解析と味物質評価への可能性2021

    • Author(s)
      山下敦子
    • Organizer
      感覚研究コンソーシアム・第 1 回味覚ワーキンググループ
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] タイプ1型味覚受容体細胞外領域に対する1価カチオン結合の構造生物学・生物物理学的解析2021

    • Author(s)
      山下敦子
    • Organizer
      日本味と匂学会第55回大会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] フグ由来味覚受容体T1R1/T1R3リガンド結合領域の試料調製とリガンド結合解析2021

    • Author(s)
      溝口 楽人,吉田 高志,細谷 麻以子,伊藤 千晶,芦川 雄二,安井 典久,山下 敦子
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] メダカ由来味覚受容体T1R2a/3細胞外領域のリガンド非結合状態における立体構造解析2021

    • Author(s)
      新田純矢、廣瀬未果、加藤貴之、山下敦子
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] メダカ受容体構造に見る味覚受容体の呈味分子認識2021

    • Author(s)
      山下敦子
    • Organizer
      第15 回食香粧研究会シンポジウム
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Coordination chemogenetics for artificially controlling neurotransmitter receptor function2021

    • Author(s)
      Shigeki Kiyonaka
    • Organizer
      Pacifichem2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 新たな配位ケモジェネティクス(1): タンパク質構造変化の干渉に基づくグルタミン酸受容体の活性制御法開発2021

    • Author(s)
      三浦 裕太、小島 憲人、浜地 格、清中 茂樹
    • Organizer
      日本化学会第101春季年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Structural and biophysical analysis of ion-binding to the extracellular ligand-binding domains of a fish taste receptor T1r2a/T1r32020

    • Author(s)
      Atsuko Yamashita, Chiaki Ito, Yuriko Takashina, Nanako Atsumi, Norihisa Yasui
    • Organizer
      International symposium on olfaction and taste (ISOT2020)
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 味覚受容体リガンド結合ドメイン-細胞外イオン相互作用の構造基盤2020

    • Author(s)
      山下敦子
    • Organizer
      第93回日本生化学会大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 配位ケモジェネティクスによる細胞種・サブタイプ選択的なグルタミン酸受容体の活性阻害法開発2020

    • Author(s)
      三浦 裕太、小島 憲人、美野 丈晴、浜地 格、清中 茂樹
    • Organizer
      第14回バイオ関連化学シンポジウム
    • Related Report
      2020 Annual Research Report
  • [Book] おいしさの科学とフードテック最前線2022

    • Author(s)
      山下敦子(都甲潔監修)
    • Total Pages
      435
    • Publisher
      シーエムシー出版
    • ISBN
      9784781316758
    • Related Report
      2022 Annual Research Report
  • [Book] 膜タンパク質工学ハンドブック2020

    • Author(s)
      津本浩平、浜窪隆雄(監修)
    • Total Pages
      624
    • Publisher
      (株)エヌ・ティー・エス
    • ISBN
      9784860435370
    • Related Report
      2020 Annual Research Report
  • [Remarks] 食塩に含まれる塩化物イオンは、甘味受容体に作用し甘味を引き起こす

    • URL

      http://www.okayama-u.ac.jp/tp/release/release_id1055.html

    • Related Report
      2022 Annual Research Report

URL: 

Published: 2020-04-28   Modified: 2024-01-30  

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