Sen Taner Z, Kloster Margaret, Jernigan Robert L, Kolinski Andrzej, Bujnicki Janusz M, Kloczkowski Andrzej
L. H. Baker Center for Bioinformatics and Biological Statistics, Iowa State University, Ames, Iowa IA50011-3260, USA.
Biophys J. 2008 Apr 1;94(7):2482-91. doi: 10.1529/biophysj.107.116046. Epub 2008 Jan 4.
Escherichia coli requires an efficient transport and signaling system to successfully sequester iron from its environment. FecA, a TonB-dependent protein, serves a critical role in this process: first, it binds and transports iron in the form of ferric citrate, and second, it initiates a signaling cascade that results in the transcription of several iron transporter genes in interaction with inner membrane proteins. The structure of the plug and barrel domains and the periplasmic N-terminal domain (NTD) are separately available. However, the linker connecting the plug and barrel and the NTD domains is highly mobile, which may prevent the determination of the FecA structure as a whole assembly. Here, we reduce the conformation space of this linker into most probable structural models using the modeling tool CABS, then apply normal-mode analysis to investigate the motions of the whole structure of FecA by using elastic network models. We relate the FecA domain motions to the outer-inner membrane communication, which initiates transcription. We observe that the global motions of FecA assign flexibility to the TonB box and the NTD, and control the exposure of the TonB box for binding to the TonB inner membrane protein, suggesting how these motions relate to FecA function. Our simulations suggest the presence of a communication between the loops on both ends of the protein, a signaling mechanism by which a signal could be transmitted by conformational transitions in response to the binding of ferric citrate.
大肠杆菌需要一个高效的转运和信号系统，以便从其周围环境中成功摄取铁。FecA是一种依赖TonB的蛋白，在这一过程中发挥关键作用：其一，它以柠檬酸铁的形式结合并转运铁；其二，它启动一个信号级联反应，该反应导致几个铁转运蛋白基因与内膜蛋白相互作用而转录。塞子结构域和桶状结构域以及周质N端结构域（NTD）的结构是分别已知的。然而，连接塞子结构域与桶状结构域以及NTD结构域的连接子具有高度的灵活性，这可能会阻碍对FecA整体组装结构的确定。在这里，我们使用建模工具CABS将该连接子的构象空间简化为最可能的结构模型，然后应用正常模式分析，通过弹性网络模型来研究FecA整体结构的运动。我们将FecA结构域的运动与启动转录的外膜-内膜通讯联系起来。我们观察到，FecA的整体运动赋予了TonB盒和NTD灵活性，并控制了TonB盒与TonB内膜蛋白结合时的暴露情况，这表明了这些运动与FecA功能之间的关系。我们的模拟表明，蛋白质两端的环之间存在通讯，这是一种信号传导机制，通过这种机制，信号可以响应柠檬酸铁的结合通过构象转变来传递。
