Cooperative Binding and Activation of Fibronectin by a Bacterial Surface Protein
Cooperative Binding and Activation of Fibronectin by a Bacterial Surface Protein
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DOI：
10.1074/jbc.m110.183053
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发表时间：
2011-01-21
影响因子：
4.8
通讯作者：
Schwarz-Linek, Ulrich
中科院分区：
文献类型：
--
作者：
Marjenberg, Zoe R.;Ellis, Ian R.;Schwarz-Linek, Ulrich
一些病原菌的整合素依赖的细胞侵袭是由针对细胞外基质蛋白纤维连接蛋白(FN)的表面蛋白介导的。虽然细菌FN识别的结构基础已经被很好地理解，但为什么像链球菌SfbI这样的蛋白质含有几个FN结合位点还不清楚。我们用微量热法揭示了FN片段与SfbI中一系列结合位点的协同结合。结合热力学分析，基于功能细胞的分析表明，SfbI诱导FN(FN100 KDa)N端100 kDa区域的构象变化，很可能是通过竞争与分子内相互作用定义FN100 kDa的非活性状态。这项研究提供了关于细菌病原体可能触发FN激活的长时间构象变化的见解。
Integrin-dependent cell invasion of some pathogenic bacteria is mediated by surface proteins targeting the extracellular matrix protein fibronectin (FN). Although the structural basis for bacterial FN recognition is well understood, it has been unclear why proteins such as streptococcal SfbI contain several FN-binding sites. We used microcalorimetry to reveal cooperative binding of FN fragments to arrays of binding sites in SfbI. In combination with thermodynamic analyses, functional cell-based assays show that SfbI induces conformational changes in the N-terminal 100-kDa region of FN (FN100kDa), most likely by competition with intramolecular interactions defining an inactive state of FN100kDa. This study provides insights into how long range conformational changes resulting in FN activation may be triggered by bacterial pathogens.