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How do alpha4-galactosyltransferases distinguish glycoproteins/glycolipids as substrates?

Research Project

Project/Area Number 20K06520
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 43020:Structural biochemistry-related
Research InstitutionNagoya City University (2023)
Niigata University (2020)

Principal Investigator

Suzuki Noriko  名古屋市立大学, 大学院薬学研究科, 研究員 (50401237)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords糖転移酵素 / 糖タンパク質 / 糖脂質 / 基質特異性 / 志賀毒素 / 糖鎖 / 遺伝子重複 / 進化 / 鳥類
Outline of Research at the Start

①α4GalT1とα4GalT2の可溶型キメラ体を用いて酵素活性に寄与する部位を同定する。次に、②細胞内の局在に寄与する細胞質領域および膜貫通領域を含めた全長キメラ体を細胞に発現し、細胞表面の糖タンパク質/糖脂質の変化を特異的抗体と糖鎖構造解析で確認し、基質特異性に寄与する配列を同定する。さらに、③得られたキメラ体とα4GalT1の活性制御分子との相互作用を調べ、基質特異性における制御分子の影響を明らかにする。

Outline of Final Research Achievements

α4-Galactosyltransferases (α4GalTs) produce Galα1-4Gal on the cell surface. While pigeon α4GalT1 and human α4GalT act on glycolipids, pigeon α4GalT2 acts mainly on glycoproteins. In this study, we compared the sequences of pigeon α4GalT1 and α4GalT2, and identified the sites on the enzymes necessary for substrate discrimination. Furthermore, similar to pigeon α4GalT1, the substrate specificity of human α4GalT was successfully converted by simultaneously replacing several specific amino acid residues on this enzyme.

Academic Significance and Societal Importance of the Research Achievements

細胞表面上の糖鎖は主に糖タンパク質や糖脂質など複合糖質として存在し、細胞接着や分子間相互作用、病原体の感受性などに影響する。糖鎖配列が類似でも非糖鎖部位が異なれば、その役割も異なる場合がある。したがって、細胞表面上のある特定の糖鎖配列を糖タンパク質や糖脂質の一方あるいは両方に自由に付加できる技術があれば、糖鎖工学技術の発展に繋がる。得られた知見を基に細胞表面上の糖鎖構造を改変することが可能となり遺伝子治療や感染症対策に役立ち、社会的な利用価値も高まる。

Report

(2 results)
  • 2023 Final Research Report ( PDF )
  • 2020 Research-status Report
  • Research Products

    (4 results)

All 2021 2020

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (1 results)

  • [Journal Article] Toward robust N-glycomics of various tissue samples that may contain glycans with unknown or unexpected structures2021

    • Author(s)
      Suzuki Noriko、Abe Tatsuya、Hanzawa Ken、Natsuka Shunji
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1

    • DOI

      10.1038/s41598-021-84668-x

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Blood group P1 antigen?bearing glycoproteins are functional but less efficient receptors of Shiga toxin than conventional glycolipid-based receptors2020

    • Author(s)
      Morimoto K, Suzuki N, Tanida I, Kakuta S, Furuta Y, Uchiyama Y, Hanada K, Suzuki Y, Yamaji T.
    • Journal Title

      J Biol Chem

      Volume: 295 Issue: 28 Pages: 9490-9501

    • DOI

      10.1074/jbc.ra120.013926

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sequential modifications of glycans by linkage-specific alkylamidation of sialic acids and permethylation2020

    • Author(s)
      Abe Tatsuya、Kameyama Akihiko、Natsuka Shunji、Suzuki Noriko
    • Journal Title

      Analytical Biochemistry

      Volume: 606 Pages: 113861-113861

    • DOI

      10.1016/j.ab.2020.113861

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] P1糖鎖エピトープを有する糖タンパク質の志賀毒素受容体としての機能解析2020

    • Author(s)
      森本貫太、鈴木詔子、谷田以誠、角田宗一郎、古田陽子、内山安男、花田賢太郎、鈴木佑典、山地俊之
    • Organizer
      日本糖質学会
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2025-01-30  

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