BINDING OF HEPARIN TO BASIC FIBROBLAST GROWTH-FACTOR INDUCES A CONFORMATIONAL CHANGE
BINDING OF HEPARIN TO BASIC FIBROBLAST GROWTH-FACTOR INDUCES A CONFORMATIONAL CHANGE
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DOI：
10.1016/0003-9861(92)90401-h
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发表时间：
1992-03-01
影响因子：
3.9
通讯作者：
ARAKAWA, T
中科院分区：
文献类型：
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作者：
PRESTRELSKI, SJ;FOX, GM;ARAKAWA, T
肝素与碱性成纤维细胞生长因子（bFGF）的结合诱导了在蛋白质红外光谱的酰胺I区域中可观察到的小但高度可重复的构象变化。观察到的光谱变化表明，构象变化是高度本地化的最有可能在β-转角区的bFGF分子。还观察到硫酸乙酰肝素（内皮细胞外基质的一种组分）与bFGF结合，并诱导与肝素观察到的构象变化相似的构象变化。此外，还观察到蔗糖八硫酸酯（一种在生物学上模拟肝素作用的化合物）诱导这种相同的构象变化。这种光谱可观察到的变化，使我们能够探测肝素结合bFGF和诱导观察到的构象变化所需的功能决定因素。我们已经确定了各种单体和聚合物，硫酸化和非硫酸化糖胺聚糖和碳水化合物的结合的影响。结果表明，肝素的结合涉及高度特异性的相互作用。此外，观察到肝素大大增加bFGF的热稳定性，使Tm提高25 °C。蔗糖八硫酸酯也能够提高bFGF的热稳定性，但没有达到与肝素相同的程度。
The binding of heparin to basic fibroblast growth factor (bFGF) induces a small but highly reproducible conformational change observable in the amide I region of the protein's infrared spectrum. The observed spectral changes suggest that the conformational change is highly localized most likely in the β-turn regions of the bFGF molecule. Heparan sulfate, a component of the endothelial extracellular matrix, was also observed to bind to bFGF and induce a similar conformational change to that observed for heparin. Further, sucrose octasulfate, a compound which mimics the effects of heparin biologically, was also observed to induce this same conformational change. This spectroscopically observable change has allowed us to probe the functional determinants necessary for heparin to bind to bFGF and to induce the observed conformational change. We have determined the effects of binding of various monomeric and polymeric, sulfated and nonsulfated glycosaminoglycans and carbohydrate compounds. The results indicate that the binding of heparin involves highly specific interactions. Further, heparin was observed to greatly increase the thermal stability of bFGF, raising theTmby 25 °C. Sucrose octasulfate was also able to enhance the thermal stability of bFGF, but not to the same extent as heparin.