Interactions between fibronectin and chondroitin sulfate are modulated by molecular context.
Interactions between fibronectin and chondroitin sulfate are modulated by molecular context.
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DOI：
10.1016/s0021-9258(17)41727-3
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发表时间：
1994-02
期刊：
影响因子：
--
通讯作者：
F. Barkalow;J. Schwarzbauer
中科院分区：
文献类型：
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作者：
F. Barkalow;J. Schwarzbauer
纤维连接蛋白(FN)和糖胺多糖之间的相互作用对细胞外基质的形态和细胞黏附是必不可少的。最丰富的糖胺多聚糖之一是硫酸软骨素，我们在这里证明了含有羧基末端细胞、肝素和纤维蛋白结构域的重组FN(Deminectins，DN)在亲和层析分析中与硫酸软骨素特异结合。利用一组突变的DN，硫酸软骨素结合的重要决定因素已定位于肝素结构域中的重复III13和III14。特别是，重复序列III13中的精氨酸对突变为中性残基使其与硫酸软骨素的结合减弱(Barkalow，F.J.B.和Schwarzbauer，J.E.(1991)J.Biol)。化学。266、7812-7818)。这些结果，结合肝素和硫酸软骨素竞争与DNS结合的能力，证明了这两种糖胺聚糖与FN中相似或重叠的部位相互作用。FN与肝素和硫酸软骨素相互作用的一个重要区别是，虽然FN和DNS与肝素的结合相同，但FN与硫酸软骨素的结合效率低于DNS。与硫酸软骨素的结合也减少了，缺少内部重复序列III1-7的较大重组FN表明氨基末端区域限制了与羧基末端结构域的结合。我们的结果表明，FN和硫酸软骨素之间的相互作用受分子背景的调控。
Interactions between fibronectin (FN) and glycosaminoglycans are essential for extracellular matrix morphology and cell adhesion. One of the most abundant glycosaminoglycans is chondroitin sulfate, and here we show that recombinant FNs (deminectins (DN)) containing the carboxyl-terminal cell, heparin, and fibrin domains bind specifically to chondroitin sulfate in affinity chromatography assays. Using a panel of mutant DNs, important determinants for chondroitin sulfate binding have been localized to repeats III13 and III14 within the heparin domain. In particular, mutation of an arginine pair in repeat III13 to neutral residues ablated binding to chondroitin sulfate as we previously reported for heparin (Barkalow, F.J.B., and Schwarzbauer, J.E. (1991) J. Biol. Chem. 266, 7812-7818). These results, in combination with the ability of heparin and chondroitin sulfate to compete for binding to DNs, demonstrate that these two glycosaminoglycans interact with similar or overlapping sites in FN. One important difference between FN interactions with heparin and chondroitin sulfate is that, while FN and DNs bound equally to heparin, FN bound less efficiently than DNs to chondroitin sulfate. Reduced binding to chondroitin sulfate was also observed with a larger recombinant FN lacking internal repeats III1-7 indicating that the amino-terminal region acts to limit binding to the carboxyl-terminal domain. Our results demonstrate that interactions between FN and chondroitin sulfate are modulated by molecular context.