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2017 年度 実績報告書

Thermodynamic basis of life: protein-carbohydrate interaction

研究課題

研究課題/領域番号 15K06962
研究機関九州大学

研究代表者

CAAVEIRO Jose  九州大学, 薬学研究院, 准教授 (00536732)

研究期間 (年度) 2015-04-01 – 2018-03-31
キーワードglycan / sugar / antibody / enzyme / pore forming protein / X-ray crystallography / Thermodynamics / kinetics
研究実績の概要

1. Overall the project has surpassed the initial goals as I reason below, which leads me to affirm that this project has been a success. The scientific output until now comprises 15 papers and 11 presentations at international conferences and venues (invited, oral and posters), and it is very likely will increase as I publish more of the results obtained. This more than doubles the initial goal.
2. The project was also extended to study the effect of glycan in additional models systems, like antibodies and human protein OMD in collaboration with Professor Kouhei Tsumoto from The University of Tokyo.
3. The results show the importance of carbohydrates in a number of proteins, and dissect the energetic basis of their interaction. For example, we discovered that sugars can mimic lipids and recognize with low affinity a lipid-binding site. This could be an ancient mechanism of certain proteins to recognize a broad spectrum of cellular surfaces, since lipids and carbohydrates appear both on the external surface of cells.
4. In antibodies, the glycan moiety attached to the Fc region has a very subtle but key importance for the recognition of the cellular receptor Fcgamma. Although the sugar does not contact the receptor it influences the binding of the antibody to it. How? The glycan regulates the flexibility of the antibody, with longer glycans reducing the entropy of the protein, leading to stronger affinity.

  • 研究成果

    (9件)

すべて 2018 2017

すべて 雑誌論文 (5件) (うち国際共著 5件、 査読あり 5件、 オープンアクセス 2件) 学会発表 (4件) (うち国際学会 1件、 招待講演 3件)

  • [雑誌論文] Assessing the heterogeneity of the Fc-glycan of a therapeutic antibody using an engineered FcγReceptor IIIa-immobilized column2018

    • 著者名/発表者名
      Kiyoshi, M., Caaveiro, J.M.M., Tada, M., Tamura, H., Tanaka, T., Terao, Y., Morante, K., Harazono, A., Hashii, N., Shibata, H., Kuroda, D., Nagatoishi, S., Oe, S., Ide, T., Tsumoto, K., and Ishii-Watabe, A.
    • 雑誌名

      Sci. Rep.

      巻: 8 ページ: 3955

    • DOI

      10.1038/s41598-018-22199-8

    • 査読あり / オープンアクセス / 国際共著
  • [雑誌論文] Intramolecular H-bonds govern the recognition of a flexible peptide by an antibody.2018

    • 著者名/発表者名
      Miyanabe, K., Akiba, H., Kuroda, D., Nakakido, M., Kusano-Arai, O., Iwanari, H., Hamakubo, T., Caaveiro, J.M.M., and Tsumoto, K.
    • 雑誌名

      J. Biochem.

      巻: in press ページ: in press

    • DOI

      10.1093/jb/mvy032

    • 査読あり / 国際共著
  • [雑誌論文] Weak electrostatic interactions between collagen and monomeric SLRP osteomodulin govern the shape of type I collagen fibrils2018

    • 著者名/発表者名
      Tashima, T., Nagatoishi, S., Caaveiro, J.M.M., Nakakido, M., Sagara, H., Mimuro, H., Ohnuma, S-I., and Tsumoto, K.
    • 雑誌名

      Commun. Biol.

      巻: 1 ページ: 33

    • DOI

      10.1038/s42003-018-0038-2

    • 査読あり / オープンアクセス / 国際共著
  • [雑誌論文] Glycosylation of IgG-Fc: a molecular perspective2017

    • 著者名/発表者名
      Kiyoshi Masato、Tsumoto Kouhei、Ishii-Watabe Akiko、Caaveiro Jose M M
    • 雑誌名

      International Immunology

      巻: 29 ページ: 311~317

    • DOI

      10.1093/intimm/dxx038

    • 査読あり / 国際共著
  • [雑誌論文] Hemolytic actinoporins interact with carbohydrates using their lipid-binding module2017

    • 著者名/発表者名
      Tanaka, K., Caaveiro, J.M.M., Morante, K., and Tsumoto, K.
    • 雑誌名

      Philos. Trans. R. Soc. Lond. B Biol. Sci.

      巻: 372 ページ: 20160216

    • DOI

      10.1098/rstb.2016.0216

    • 査読あり / 国際共著
  • [学会発表] Molecular recognition phenomena involving proteins of therapeutic interest.2017

    • 著者名/発表者名
      Caaveiro J.M.M.
    • 学会等名
      3rd HU-TMU-KU Joint Symposium for Pharmaceutical Sciences
    • 招待講演
  • [学会発表] Protein-lipid interactions in a pore-forming toxin.2017

    • 著者名/発表者名
      Tsumoto, K. and Caaveiro, J.M.M.
    • 学会等名
      55th Annual Meeting of the Biophysical Society of Japan
    • 招待講演
  • [学会発表] Caaveiro, J.M.M., Kiyoshi, M., Ueda, T., and Tsumoto, K.2017

    • 著者名/発表者名
      Structural Biology of Fc receptors.
    • 学会等名
      Antibody Engineering & Therapeutics (Annual meeting of the Antibody Society)
    • 国際学会
  • [学会発表] The Fascinating journey of a metamorphic protein to the cell membrane2017

    • 著者名/発表者名
      Caaveiro, J.M.M.
    • 学会等名
      Bioforo 5th Alumni Research Meeting
    • 招待講演

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公開日: 2018-12-17  

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