Solution NMR structure of a human FGF-1 monomer, activated by a hexasaccharide heparin-analogue

Angeles Canales, Rosa Lozano, Blanca López-Méndez, Jesús Angulo, Rafael Ojeda, Pedro M. Nieto, Manuel Martín-Lomas, Guillermo Giménez-Gallego, Jesús Jiménez-Barbero

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Abstract

The 3D structure of a complex formed by the acidic fibroblast growth factor (FGF-1) and a specifically designed synthetic heparin hexasaccharide has been determined by NMR spectroscopy. This hexasaccharide can substitute natural heparins in FGF-1 mitogenesis assays, in spite of not inducing any apparent dimerization of the growth factor. The use of this well defined synthetic heparin analogue has allowed us to perform a detailed NMR structural analysis of the heparin-FGF interaction, overcoming the limitations of NMR to deal with the high molecular mass and heterogeneity of the FGF-1 oligomers formed in the presence of natural heparin fragments. Our results confirm that glycosaminoglycans induced FGF-1 dimerization either in a cis or trans disposition with respect to the heparin chain is not an absolute requirement for biological activity.
Original languageEnglish
Pages (from-to)4716-4727
Number of pages12
JournalFEBS Journal
Volume273
Issue number20
DOIs
Publication statusPublished - 1 Oct 2006

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