Fibrillin-1 interactions with heparin - Implications for microfibril and elastic fiber assembly
Fibrillin-1 interactions with heparin - Implications for microfibril and elastic fiber assembly
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DOI：
10.1074/jbc.m501390200
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发表时间：
2005-08-26
影响因子：
4.8
通讯作者：
Kielty, CM
中科院分区：
文献类型：
--
作者：
Cain, SA;Baldock, C;Kielty, CM
原纤维蛋白-1组装成微纤维和弹性纤维的形成涉及与糖胺聚糖的相互作用。我们已经使用BIAcore技术来研究与肝素和与类似于硫酸乙酰肝素的S-结构域的肝素结合蛋白-1相互作用。我们已经确定了四个高亲和力的肝素结合位点上的肝素-1，本地化这些网站中的三个，并确定其结合动力学。肝素结合到肝素-1 N末端具有特别快的动力学。Hybryononan和硫酸软骨素没有显着的相互作用，与β-淀粉样蛋白-1。含有超过12个单糖单元的肝素β与所有四个β-内酰胺酶-1位点强烈结合。肝素不抑制β-内酰胺酶-1 N-和C-末端相互作用或RGD依赖性细胞附着，但肝素和MAGP-1竞争结合β-内酰胺酶-1 N末端，肝素和弹性蛋白原竞争结合中央β-内酰胺酶-1序列。通过调节这些关键的相互作用，肝素可以深刻地影响微纤维和弹性纤维组装。
Fibrillin-1 assembly into microfibrils and elastic fiber formation involves interactions with glycosaminoglycans. We have used BIAcore technology to investigate fibrillin-1 interactions with heparin and with heparin saccharides that are analogous to S-domains of heparan sulfate. We have identified four high affinity heparin-binding sites on fibrillin-1, localized three of these sites, and defined their binding kinetics. Heparin binding to the fibrillin-1 N terminus has particularly rapid kinetics. Hyaluronan and chondroitin sulfate did not interact significantly with fibrillin-1. Heparin saccharides with more than 12 monosaccharide units bound strongly to all four fibrillin-1 sites. Heparin did not inhibit fibrillin-1 N- and C-terminal interactions or RGD-dependent cell attachment, but heparin and MAGP-1 competed for binding to the fibrillin-1 N terminus, and heparin and tropoelastin competed for binding to a central fibrillin-1 sequence. By regulating these key interactions, heparin can profoundly influence microfibril and elastic fiber assembly.