The tandem β-zipper model defines high affinity fibronectin-binding repeats within staphylococcus aureus FnBPA
The tandem β-zipper model defines high affinity fibronectin-binding repeats within staphylococcus aureus FnBPA
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DOI：
10.1074/jbc.m703063200
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发表时间：
2007-08-31
影响因子：
4.8
通讯作者：
Potts, Jennifer R.
中科院分区：
文献类型：
--
作者：
Meenan, Nicola A. G.;Visai, Livia;Potts, Jennifer R.
金黄色葡萄球菌的纤维连接蛋白结合蛋白FnBPA与人蛋白纤维连接蛋白的结合先前已被认为与感染性心内膜炎的发展有关，特别是在血小板活化和内皮浸润的过程中。我们最近提出了一种纤维连接蛋白与FnBPA结合的模型，其中细菌蛋白含有11个潜在的结合位点（FnBPA-1至FnBPA11），每个位点由结合在纤维连接蛋白n端结构域中连续的纤维连接蛋白1型模块的基元组成。在这里，我们发现11个位点中有6个结合的解离常数在纳摩尔范围内；其他位点的结合更弱。高亲和力结合位点包括FnBPA-1，其序列先前被认为包含在FnBPA的纤维蛋白原结合A结构域中。1型模块结合基序的数量和序列守恒对于高亲和结合很重要。体外结合研究的体内相关性被金黄色葡萄球菌感染患者中存在的抗体所证实，这些抗体特异性识别这六个高亲和力重复序列与纤维连接蛋白的复合物。
Binding of the fibronectin-binding protein FnBPA from Staphylococcus aureus to the human protein fibronectin has previously been implicated in the development of infective endocarditis, specifically in the processes of platelet activation and invasion of the endothelium. We recently proposed a model for binding of fibronectin to FnBPA in which the bacterial protein contains 11 potential binding sites (FnBPA-1 to FnBPA11), each composed of motifs that bind to consecutive fibronectin type 1 modules in the N-terminal domain of fibronectin. Here we show that six of the 11 sites bind with dissociation constants in the nanomolar range; other sites bind more weakly. The high affinity binding sites include FnBPA-1, the sequence of which had previously been thought to be encompassed by the fibrinogen-binding A domain of FnBPA. Both the number and sequence conservation of the type-1 module binding motifs appears to be important for high affinity binding. The in vivo relevance of the in vitro binding studies is confirmed by the presence of antibodies in patients with S. aureus infections that specifically recognize complexes of these six high affinity repeats with fibronectin.