TY - JOUR
T1 - Solution NMR structure of a human FGF-1 monomer, activated by a hexasaccharide heparin-analogue
AU - Canales, Angeles
AU - Lozano, Rosa
AU - López-Méndez, Blanca
AU - Angulo, Jesús
AU - Ojeda, Rafael
AU - Nieto, Pedro M.
AU - Martín-Lomas, Manuel
AU - Giménez-Gallego, Guillermo
AU - Jiménez-Barbero, Jesús
PY - 2006/10/1
Y1 - 2006/10/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33749412368&partnerID=8YFLogxK
U2 - 10.1111/j.1742-4658.2006.05474.x
DO - 10.1111/j.1742-4658.2006.05474.x
M3 - Article
AN - SCOPUS:33749412368
VL - 273
SP - 4716
EP - 4727
JO - FEBS Journal
JF - FEBS Journal
SN - 1742-464X
IS - 20
ER -