Minimal heparin/heparan sulfate sequences for binding to fibroblast growth factor-1.
The glycosaminoglycans heparin and heparan sulfate (HS) bind to fibroblast growth factor FGF1 and promote its dimerization, a proposed prerequisite for binding to a cellular receptor and triggering mitogenic signals. The problem of minimal structural requirements for heparin/HS sequences to bind FGF1 was approached by surface plasmon resonance (SPR), NMR spectroscopy, and MALDI mass spectrometry studies using the three synthetic tetrasaccharides GlcNSO(3)6OR-IdoA2SO(3)-GlcNSO(3)6OR'-IdoA2SO(3)OPr (AA, R = R' = SO(3); BA, R = H, R' = SO(3); BB, R = R' = H; Pr, propyl). AA and BA significantly interact with the protein, whereas BB is practically inactive. The NMR spectra show that, whereas the interaction of AA primarily involves the GlcNSO(3)6SO(3)IdoA2SO(3) disaccharide moiety at its nonreducing end, residues at both the nonreducing (NR) and reducing side (R) appear to be involved in the weaker complex of BA. Furthermore, MALDI experiments show that, in addition to 1:1 protein:tetrasaccharide complexes, AA and BA are able to form 2:1 complexes, indicating that heparin/HS-induced dimerization of FGF1 requires only one 6-OSO(3) group per tetrasaccharide.
Guerrini
Marco
M
Institute for Chemical and Biochemical Research G. Ronzoni, via G. Colombo 81, 20133 Milan, Italy.
Agulles
Teresa
T
Bisio
Antonella
A
Hricovini
Milos
M
Lay
Luigi
L
Naggi
Annamaria
A
Poletti
Laura
L
Sturiale
Luisella
L
Torri
Giangiacomo
G
Casu
Benito
B
D001667:Binding, Competitive; D002240:Carbohydrate Sequence; D019281:Dimerization; D016220:Fibroblast Growth Factor 1 / Q000737:chemistry / Q000378:metabolism*; D006493:Heparin / Q000737:chemistry* / Q000378:metabolism*; D006497:Heparan Sulfate / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D020349:Surface Plasmon Resonance
D016220:Fibroblast Growth Factor 1; D006493:Heparin; D006497:Heparan Sulfate; D009844:Oligosaccharides