Substrate-receptor interactions in the Tat protein transport pathway

所有细菌都会产生作用于细菌细胞外部的蛋白质。细菌病原体产生的毒素就是一个很好的例子。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通常不渗透的细胞膜，被移出细胞。这项任务是由位于细胞膜上的蛋白质转运体来完成的。Tat蛋白转运体存在于许多不同的细菌中，包括几乎所有导致人类疾病的细菌，如结核分枝杆菌（导致结核病）和沙门氏菌（导致食物中毒）。在所有被检测的致病菌中，Tat转运体对细菌致病至关重要。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，并最终设计新药来阻止它的工作，该项目将使用尖端技术来阐明运输机制如何识别存在于要运输的蛋白质上的靶向标签。我们还将测试Tat转运体通过移动标签穿过膜来工作的假设，并将客运蛋白拉到它后面。

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, and ultimately to design new drugs to stop it working, this project will use cutting edge technology to elucidate how the transport machinery recognises the targeting tags present on the proteins that are to be transported. We will also test the hypothesis that the Tat transporter works by moving the tag across the membrane and that this pulls the passenger protein after it.