Triggering assembly of the twin-arginine translocase

所有的细菌都会产生在细菌细胞外运作的蛋白质。细菌病原体产生的毒素就是很好的例子。由于细菌只在细胞内制造蛋白质，新合成的细胞外蛋白质必须穿过正常不透水的细胞膜移出细胞。这项任务是由位于细胞膜上的被称为蛋白质转运体的机器完成的。Tat蛋白转运体存在于许多不同的细菌中，包括几乎所有引起人类疾病的细菌，如引起结核病的结核分枝杆菌和引起食物中毒的沙门氏菌。在所有被测试的致病细菌中，TAT转运蛋白是细菌致病的关键。因此，科学家们对开发阻止TAT系统工作的药物越来越感兴趣。为了了解TAT机制是如何工作的，我们将使用尖端的分子建模、动力学和实验方法来阐明运输机制如何识别要运输的蛋白质上的靶向标签。这一知识将有助于支持理解和抑制病原体中这一途径的尝试。

All bacteria produce proteins that operate on the outside of the bacterial cell. Good examples of this are the toxins produced by bacterial pathogens. Since bacteria only make proteins inside the cell, the newly-synthesised extracellular proteins must be moved out of the cell across the normally impermeable cell membrane. This task is carried out by machines termed protein transporters that are located in the cell membrane.The Tat protein transporter is found in many different bacteria including almost all those which cause human diseases such as Mycobacterium tuberculosis (which causes tuberculosis), and Salmonella (which causes food poisoning). In all pathogenic bacteria tested the Tat transporter is essential for the bacterium to cause disease. Thus, scientists are becoming increasingly interested in developing drugs that prevent the Tat system from working.In order to understand how the Tat machinery works we will use cutting edge molecular modelling, dynamics and experimental approaches to elucidate how the transport machinery recognises the targeting tags present on the proteins that are to be transported. This knowledge will help underpin attempts to understand and inhibit this pathway in pathogens.