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Solution structure of human acidic fibroblast growth factor and interaction with heparin-derived hexasaccharide

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Abstract

Fibroblast growth factors (FGFs) bind to extracellular matrices, especially heparin-like carbohydrates of heparansulfate proteoglycans which stabilize FGFs to protect against inactivation by heat, acid, proteolysis and oxidation. Moreover, binding of FGFs to cell surface proteoglycans promotes to form oligomers, which is essential for receptor oligomerization and activation. In the present study, we determined the solution structure of acidic FGF using a series of triple resonance multi-dimensional NMR experiments and simulated annealing calculations. Furthermore, we prepared the sample complexed with a heparin-derived hexasaccharide which is a minimum unit for aFGF binding. From the chemical shift differences between free aFGF and aFGF-heparin complex, we concluded that the major heparin binding site was located on the regions 110–131 and 17–21. The binding sites are quite similar to those observed for bFGF-heparin hexasaccharide complex, showing that both FGFs recognize heparin- oligosaccharides in a similar manner.

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Authors and Affiliations

  1. Department of Molecular Physiology, Tokyo Metropolitan Institute of Medical Science, Tokyo, 113-8613, Japan

    Kenji Ogura, Koji Nagata, Hideki Hatanaka & Fuyuhiko Inagaki

  2. Molecular Medical Laboratory, Aichi Medical School, Aichi, 480- 1195, Japan

    Hiroko Habuchi & Koji Kimata

  3. Department of Chemistry, Faculty of Science, Tokyo Metropolitan University, Tokyo, 192-0397, Japan

    Shin-ichi Tate

  4. Rhone-Poulenc Rorer Central Research, PA, 19406, U.S.A.

    Mark W. Ravera & Michael Jaye

  5. Department of Pharmacology, New York University Medical Center, New York, NY, 10016, U.S.A.

    J. Schlessinger

Authors
  1. Kenji Ogura
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  2. Koji Nagata
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  3. Hideki Hatanaka
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  4. Hiroko Habuchi
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  8. Michael Jaye
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  10. Fuyuhiko Inagaki
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Ogura, K., Nagata, K., Hatanaka, H. et al. Solution structure of human acidic fibroblast growth factor and interaction with heparin-derived hexasaccharide. J Biomol NMR 13, 11–24 (1999). https://doi.org/10.1023/A:1008330622467

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