Guerrini Marco, Agulles Teresa, Bisio Antonella, Hricovini Milos, Lay Luigi, Naggi Annamaria, Poletti Laura, Sturiale Luisella, Torri Giangiacomo, Casu Benito
Institute for Chemical and Biochemical Research G. Ronzoni, via G. Colombo 81, 20133 Milan, Italy.
Biochem Biophys Res Commun. 2002 Mar 22;292(1):222-30. doi: 10.1006/bbrc.2002.6634.
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.
糖胺聚糖肝素和硫酸乙酰肝素（HS）与成纤维细胞生长因子FGF1结合并促进其二聚化，这是与细胞受体结合并触发促有丝分裂信号的一个假定前提条件。通过表面等离子体共振（SPR）、核磁共振光谱和基质辅助激光解吸电离质谱研究，利用三种合成四糖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，丙基）来探讨肝素/HS序列结合FGF1的最小结构要求问题。AA和BA与该蛋白有显著相互作用，而BB实际上没有活性。核磁共振光谱表明，虽然AA的相互作用主要涉及非还原端的GlcNSO(3)6SO(3)IdoA2SO(3)二糖部分，但非还原端（NR）和还原端（R）的残基似乎都参与了BA较弱的复合物形成。此外，基质辅助激光解吸电离实验表明，除了1:1的蛋白:四糖复合物外，AA和BA还能够形成2:1的复合物，这表明肝素/HS诱导的FGF1二聚化每个四糖仅需要一个6-OSO(3)基团。
