Ogura K, Nagata K, Hatanaka H, Habuchi H, Kimata K, Tate S, Ravera M W, Jaye M, Schlessinger J, Inagaki F
Department of Molecular Physiology, Tokyo Metropolitan Institute of Medical Science, Japan.
J Biomol NMR. 1999 Jan;13(1):11-24. doi: 10.1023/a:1008330622467.
Fibroblast growth factors (FGFs) bind to extracellular matrices, especially heparin-like carbohydrates of heparan-sulfate proteoglycans which stabilize FGFs to protect against inactivation by heat, acid, proteolysis and oxidation. Moreover, binding of FGFs to cell surface proteoglycans promotes to form oligomers, which is essential for receptor oligomerization and activation. In the present study, we determined the solution structure of acidic FGF using a series of triple resonance multi-dimensional NMR experiments and simulated annealing calculations. Furthermore, we prepared the sample complexed with a heparin-derived hexasaccharide which is a minimum unit for aFGF binding. From the chemical shift differences between free aFGF and aFGF-heparin complex, we concluded that the major heparin binding site was located on the regions 110-131 and 17-21. The binding sites are quite similar to those observed for bFGF-heparin hexasaccharide complex, showing that both FGFs recognize heparin-oligosaccharides in a similar manner.
成纤维细胞生长因子（FGFs）与细胞外基质结合，尤其是硫酸乙酰肝素蛋白聚糖的类肝素碳水化合物，后者可稳定FGFs，保护其免受加热、酸、蛋白水解和氧化作用而失活。此外，FGFs与细胞表面蛋白聚糖的结合促进形成寡聚体，这对于受体寡聚化和激活至关重要。在本研究中，我们使用一系列三重共振多维核磁共振实验和模拟退火计算确定了酸性FGF的溶液结构。此外，我们制备了与肝素衍生的六糖复合的样品，该六糖是aFGF结合的最小单位。根据游离aFGF和aFGF-肝素复合物之间的化学位移差异，我们得出结论，主要的肝素结合位点位于110-131和17-21区域。这些结合位点与bFGF-肝素六糖复合物中观察到的位点非常相似，表明两种FGFs以相似的方式识别肝素寡糖。
