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Ligand recognition mechanism by the secreted scavenger receptor AIM

Research Project

Project/Area Number 17H02200
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biomolecular chemistry
Research InstitutionOita University (2018-2019)
The University of Tokyo (2017)

Principal Investigator

Matsuoka Shigeru  大分大学, 医学部, 特任准教授 (60456184)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2019: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
Keywordsスカベンジャー受容体 / 分子認識 / 活性酸素 / 分子機構 / 低分子 / 自然免疫 / マクロファージ
Outline of Final Research Achievements

AIM has been attracting attention as a drug candidate for renal failure in cats. In this research, we performed chemical investigation on the molecular mechanism of AIM and revealed that one of the various biological functions of AIM is the inhibitory action to the generation of reactive oxygen species (ROS) by free iron. Furthermore, based on the molecular structure of AIM, we designed and synthesized a peptide with a molecular weight of about 1200 and a low molecule with a molecular weight of about 500, which possess inhibitory effect on the generation of ROS by free iron.

Academic Significance and Societal Importance of the Research Achievements

マクロファージによって生産されるタンパク質AIMは血流にのって全身をめぐり、体内の異物や老廃物の除去を促進することで腎不全や肝臓がんなど多様な疾患の治癒に寄与すると考えられ、注目を集めている。
本研究では、AIMが遊離鉄イオンに結合して、活性酸素の発生を防ぐことを明らかにした。さらに、分子量約42,000のAIMの部分構造から、遊離鉄の活性酸素発生阻害効果を持つ分子量約1200のペプチドおよび分子量約500の低分子化合物を見出すことができた。遊離鉄は生体内で過剰な活性酸を発生して細胞を傷つける危険な化学種としても知られている。本研究は、遊離鉄を無毒化する低分子医薬品の開発に資すると期待される。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (2 results)

All 2018 2017

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (1 results)

  • [Journal Article] The IgM pentamer is an asymmetric pentagon with an open groove that binds the AIM protein.2018

    • Author(s)
      Hiramoto E, Tsutsumi A, Suzuki R, Matsuoka S, Arai S, Kikkawa M, Miyazaki T.
    • Journal Title

      Science Advances

      Volume: 4 Issue: 10

    • DOI

      10.1126/sciadv.aau1199

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] ネコ特異的な腎疾患自己治癒機構の欠損2017

    • Author(s)
      杉澤良一, 平本絵美莉, 松岡 茂, 新井郷子, 宮崎 徹
    • Organizer
      第17回東京大学生命科学シンポジウム
    • Related Report
      2017 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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