Solution NMR structure of a human FGF-1 monomer, activated by a hexasaccharide heparin-analogue.
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.
Canales
Angeles
A
Centro de Investigaciones Biológicas,CSIC, Madrid, Spain.
Lozano
Rosa
R
López-Méndez
Blanca
B
Angulo
Jesús
J
Ojeda
Rafael
R
Nieto
Pedro M
PM
Martín-Lomas
Manuel
M
Giménez-Gallego
Guillermo
G
Jiménez-Barbero
Jesús
J
D001665:Binding Sites; D002240:Carbohydrate Sequence; D019281:Dimerization; D016220:Fibroblast Growth Factor 1 / Q000737:chemistry* / Q000378:metabolism; D006493:Heparin / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000737:chemistry; D009844:Oligosaccharides / Q000737:chemistry*; D012996:Solutions
D046912:Multiprotein Complexes; D009844:Oligosaccharides; D012996:Solutions; D016220:Fibroblast Growth Factor 1; D006493:Heparin