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Novel mechanism of glycan-mediated activation of cytokine receptors by lectins from marine sponges

Research Project

Project/Area Number 22K20589
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0603:Forestry and forest products science, applied aquatic science, and related fields
Research InstitutionHokkaido University

Principal Investigator

Watari Hiromi  北海道大学, 水産科学研究院, 助教 (30962758)

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トロンボポエチン受容体 / レクチン / 糖鎖 / 海洋天然物 / 生理活性タンパク質
Outline of Research at the Start

これまで応募者はミクロネシア産海綿に含まれる新規フコース結合性レクチンThCが,造血サイトカインのトロンボポエチンTPOと類似した活性を示すことを発見した.さらにThCのTPO受容体に対する作用機構が全く新しいものであることを立証した.加えて,ThCに酷似した構造を持つバクテリアレクチンPA-IILが,ThCに比べ非常に弱い活性を持つことを見出し,これらの構造活性相関の理解がTPO受容体の新しい活性化機構を解明する鍵であると考えた.本研究ではThCの変異体やバクテリアゲノムに埋もれているThC類似タンパク質を発掘し,構造活性相関を評価することで新規のTPO受容体活性化機構の全貌解明を目指す.

Outline of Final Research Achievements

In our previous study, we clarified the mechanism of TPO receptor activation by thrombocorticin (ThC), a novel lectin derived from a marine sponge. We have expressed here recombinant proteins of various ThC mutants to reveal the details of TPO receptor activation by lectins via glycan. It was showed that wild-type ThC exhibited by far the strongest activity, but the three-dimensional structure of the expressed lectin was almost identical to ThC using a protein three-dimensional structure prediction tool, so the definitive reason that could explain the difference in activity has not been clarified. Further investigation is required, such as structural comparison of the complex with the TPO receptor.

Academic Significance and Societal Importance of the Research Achievements

骨髄増殖性腫瘍という疾患においてThCによるTPO受容体活性化と同様の機構の存在が示唆されていたが、その詳細は不明であった。ThCによる活性化機構の解明により、TPO受容体上の糖鎖を介した活性化が、疾患の原因として実際に体内で生じていることを間接的ではあるものの、示した。本研究においてThCに類似した構造を持つレクチンがTPO受容体にどのような活性を示すかを調べることは、レクチンがTPO受容体の活性化をどのように調節しているのか、その疑問に対し新たな知見を与え、延いては未だ明らかとなっていない疾患の詳細の理解につながる。

Report

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

    (10 results)

All 2024 2023 2022

All Journal Article (5 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 2 results) Presentation (5 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results)

  • [Journal Article] 海綿レクチンで迫るトロンボポエチン受容体の多様な活性化機構の謎2024

    • Author(s)
      辺 浩美, 酒井 隆一
    • Journal Title

      化学と生物

      Volume: 62 Pages: 166-168

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dopamine-Derived Guanidine Alkaloids from a Didemnidae Tunicate: Isolation, Synthesis, and Biological Activities2024

    • Author(s)
      Sakai Ryuichi、Matsumura Ken、Uchimasu Hajime、Miyako Kei、Taniguchi Tohru、Kovvuri V. Raghavendra Rao、Acharige Anjana Delpe、Hull Kenneth G.、Romo Daniel、Thaveepornkul Lakkana、Chimnaronk Sarin、Miyamoto Hiroko、Takada Ayato、Watari Hiromi、Fujita Masaki J.、Sakaue Jiro
    • Journal Title

      The Journal of Organic Chemistry

      Volume: - Issue: 9 Pages: 5977-5987

    • DOI

      10.1021/acs.joc.3c02765

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Total synthesis of lycoperdic acid and stereoisomers (part 2): Completion of the synthesis and biological evaluation2023

    • Author(s)
      Morokuma Kenji、Watari Hiromi、Mori Maika、Sakai Ryuichi、Irie Raku、Oikawa Masato
    • Journal Title

      Tetrahedron

      Volume: 145 Pages: 133623-133623

    • DOI

      10.1016/j.tet.2023.133623

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Interaction of Polyamine-modified Marine Peptide Aculeine A with Cell Membranes: Disruption or Entry2023

    • Author(s)
      Watari Hiromi、Kishi Reimi、Matsunaga Satoko、Nishikawa Takayuki、Sawada Yuji、Honda Akito、Fujita Masaki J、Sakai Ryuichi
    • Journal Title

      Chemistry Letters

      Volume: 52 Issue: 3 Pages: 185-189

    • DOI

      10.1246/cl.230009

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] A marine sponge-derived lectin reveals hidden pathway for thrombopoietin receptor activation2022

    • Author(s)
      Watari Hiromi、Kageyama Hiromu、Masubuchi Nami、Nakajima Hiroya、Onodera Kako、Focia Pamela J.、Oshiro Takumi、Matsui Takashi、Kodera Yoshio、Ogawa Tomohisa、Yokoyama Takeshi、Hirayama Makoto、Hori Kanji、Freymann Douglas M.、Imai Misa、Komatsu Norio、Araki Marito、Tanaka Yoshikazu、Sakai Ryuichi
    • Journal Title

      Nature Communications

      Volume: 13 Issue: 1 Pages: 7262-7262

    • DOI

      10.1038/s41467-022-34921-2

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] MECHANISM OF CYTOKINE RECEPTOR ACTIVATION BY MARINE SPONGE LECTIN.2023

    • Author(s)
      Hiromi Watari, Hiroki Kageyama, Nami Masubuchi, Marito Araki, Yoshikazu Tanaka and Ryuichi Sakai
    • Organizer
      International Symposium on Marine Natural Products
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 受容体の新規活性化機構を掘り起こす海洋天然物2023

    • Author(s)
      辺浩美
    • Organizer
      化学生態学
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Cytological effects of a novel sponge derived protein toxin, soritesidine2023

    • Author(s)
      Hiromi Watari, Masaya Kitano, Yuri Ishibashi, Ryuichi Sakai
    • Organizer
      The 38th Symposium on Natural Products
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 海綿由来レクチンをプローブとしたサイトカイン受容体 新規活性化機構の解明2022

    • Author(s)
      辺浩美
    • Organizer
      第64回天然有機化合物討論会
    • Related Report
      2022 Research-status Report
  • [Presentation] 海綿由来レクチン ThC によるサイトカイン受容体 新規活性化機構の解明2022

    • Author(s)
      辺浩美
    • Organizer
      令和4年度 日本農芸化学会 北海道・東北支部 合同支部会
    • Related Report
      2022 Research-status Report

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

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