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Structure-function analysis of human bitter taste receptors

Research Project

Project/Area Number 22K20632
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0701:Biology at molecular to cellular levels, and related fields
Research InstitutionOkayama University

Principal Investigator

Tsutsumi Naotaka  岡山大学, 医歯薬学域, 助教 (70963495)

Project Period (FY) 2022-08-31 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords難生産性タンパク質 / 苦味受容体 / クライオEM / 膜タンパク質 / 受容体 / 苦味 / TAS2R / GPCR / クライオ電子顕微鏡 / 構造生物学
Outline of Research at the Start

苦味感覚は、生物が備える味覚の中でも、元来、毒物を判別するために進化してきたとされる。苦味受容体(Taste 2 Receptor: TAS2R)は、クラスTとして独立のグループを形成するGタンパク質共役受容体(GPCR)であり、ヒトは数千種類の苦味物質を、わずか25種類のTAS2Rで認識している。本研究では、この現象の分子機構と生理学的意義を解明する第一歩として、高品質組み換え発現TAS2Rの大量調製法を確立した上で、苦味物質群との結合実験を含めた物理化学的解析に取り組む。さらには、細胞内のシグナル伝達物質であるGタンパク質との安定複合体を精製し、立体構造・活性化機構解明への基盤とする。

Outline of Final Research Achievements

Bitter taste receptor TAS2Rs recognize bitter substances in taste cells and other tissues in the body and are considered to have diverse functions beyond bitter taste perception. In this study, I established expression and purification systems for various TAS2R subtypes and successfully prepared the signaling TAS2R complexes with gustducin. The recombinant TAS2Rs would be beneficial for future structural and functional analysis.

Academic Significance and Societal Importance of the Research Achievements

本研究を基盤として苦味受容体の機能研究を展開することで、将来的には食品・医薬産業への貢献が期待できる。また、本研究で開発した組換えタンパク質発現技術は他の難生産性膜タンパク質へも適用可能であり、これまで機能・構造研究が停滞していた生理学的に重要なタンパク質の研究が進展する可能性がある。

Report

(3 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • Research Products

    (16 results)

All 2024 2023 2022

All Journal Article (9 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 9 results,  Open Access: 8 results) Presentation (4 results) (of which Int'l Joint Research: 1 results,  Invited: 3 results) Book (3 results)

  • [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
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Structural insight into guanylyl cyclase receptor hijacking of the kinase?Hsp90 regulatory mechanism2023

    • Author(s)
      Caveney Nathanael A、Tsutsumi Naotaka、Garcia K Christopher
    • Journal Title

      eLife

      Volume: 12

    • DOI

      10.7554/elife.86784.3

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Structure of the thrombopoietin-MPL receptor complex is a blueprint for biasing hematopoiesis2023

    • Author(s)
      Tsutsumi Naotaka、Masoumi Zahra、James Sophie C.、Tucker Julie A.、Winkelmann Hauke、Grey William、Picton Lora K.、Moss Lucie、Wilson Steven C.、Caveney Nathanael A.、Jude Kevin M.、Gati Cornelius、Piehler Jacob、Hitchcock Ian S.、Garcia K. Christopher
    • Journal Title

      Cell

      Volume: 186 Issue: 19 Pages: 4189-4203.e22

    • DOI

      10.1016/j.cell.2023.07.037

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Structure of the Wnt-Frizzled-LRP6 initiation complex reveals the basis for coreceptor discrimination2023

    • Author(s)
      Tsutsumi Naotaka、Hwang Sunhee、Waghray Deepa、Hansen Simon、Jude Kevin M.、Wang Nan、Miao Yi、Glassman Caleb R.、Caveney Nathanael A.、Janda Claudia Y.、Hannoush Rami N.、Garcia K. Christopher
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 120 Issue: 11

    • DOI

      10.1073/pnas.2218238120

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Structural basis of Janus kinase trans-activation2023

    • Author(s)
      Caveney Nathanael A.、Saxton Robert A.、Waghray Deepa、Glassman Caleb R.、Tsutsumi Naotaka、Hubbard Stevan R.、Garcia K. Christopher
    • Journal Title

      Cell Reports

      Volume: 42 Issue: 3 Pages: 112201-112201

    • DOI

      10.1016/j.celrep.2023.112201

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Structure of a Janus kinase cytokine receptor complex reveals the basis for dimeric activation2022

    • Author(s)
      Glassman Caleb R.、Tsutsumi Naotaka、Saxton Robert A.、Lupardus Patrick J.、Jude Kevin M.、Garcia K. Christopher
    • Journal Title

      Science

      Volume: 376 Issue: 6589 Pages: 163-169

    • DOI

      10.1126/science.abn8933

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Structure of the IL-27 quaternary receptor signaling complex2022

    • Author(s)
      Caveney Nathanael A、Glassman Caleb R、Jude Kevin M、Tsutsumi Naotaka、Garcia K Christopher
    • Journal Title

      eLife

      Volume: 11

    • DOI

      10.7554/elife.78463

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Organizing structural principles of the IL-17 ligand-receptor axis2022

    • Author(s)
      Wilson Steven C.、Caveney Nathanael A.、Yen Michelle、Pollmann Christoph、Xiang Xinyu、Jude Kevin M.、Hafer Maximillian、Tsutsumi Naotaka、Piehler Jacob、Garcia K. Christopher
    • Journal Title

      Nature

      Volume: 609 Issue: 7927 Pages: 622-629

    • DOI

      10.1038/s41586-022-05116-y

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Viral G Protein-Coupled Receptors Encoded by β- and γ-Herpesviruses2022

    • Author(s)
      Rosenkilde Mette M.、Tsutsumi Naotaka、Knerr Julius M.、Kildedal Dagmar F.、Garcia K. Christopher
    • Journal Title

      Annual Review of Virology

      Volume: 9 Issue: 1 Pages: 329-351

    • DOI

      10.1146/annurev-virology-100220-113942

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Wnt-Frizzled-LRP6複合体の構造が明らかにした古典的β-カテニンシグナルの開始機構2023

    • Author(s)
      堤尚孝
    • Organizer
      第23回日本蛋白質科学年会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Structural evolution of human cytomegalovirus GPCRs US27 and US282023

    • Author(s)
      Naotaka Tsutsumi
    • Organizer
      The 4th European Chemokine and Cell Migration Conference
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] サイトカインと腫瘍性変異によるヤヌスキナーゼの活性化機構2023

    • Author(s)
      堤尚孝
    • Organizer
      日本薬学会第143年会
    • Related Report
      2022 Research-status Report
  • [Presentation] Structural mechanism of Janus kinase activation2022

    • Author(s)
      Naotaka Tsutsumi
    • Organizer
      第20回蛋白研リトリート
    • Related Report
      2022 Research-status Report
    • Invited
  • [Book] 生物物理2023年63巻6号2024

    • Author(s)
      堤尚孝
    • Total Pages
      4
    • Publisher
      日本生物物理学会
    • Related Report
      2023 Annual Research Report
  • [Book] 実験医学2024年9月号2023

    • Author(s)
      堤尚孝
    • Total Pages
      3
    • Publisher
      羊土社
    • ISBN
      9784758125772
    • Related Report
      2023 Annual Research Report
  • [Book] 実験医学2022年9月号2022

    • Author(s)
      堤尚孝
    • Total Pages
      4
    • Publisher
      羊土社
    • ISBN
      9784758125598
    • Related Report
      2022 Research-status Report

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Published: 2022-09-01   Modified: 2025-01-30  

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