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Solution NMR structure of a human FGF‐1 monomer, activated by a hexasaccharide heparin‐analogue
Author(s) -
Canales Angeles,
Lozano Rosa,
LópezMéndez Blanca,
Angulo Jesús,
Ojeda Rafael,
Nieto Pedro M.,
MartínLomas Manuel,
GiménezGallego Guillermo,
JiménezBarbero Jesús
Publication year - 2006
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2006.05474.x
Subject(s) - chemistry , heparin , monomer , stereochemistry , biochemistry , polymer , organic chemistry
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.