Exploiting the structure of the twin-arginine protein translocase core

细菌中的一些蛋白质位于包围细胞的膜外，例如细菌病原体产生的毒素。因为所有的蛋白质都是在细菌内部制造的，所以外部的蛋白质必须通过称为蛋白质转运蛋白的机器穿过通常不可渗透的细胞膜移出细胞。一种类型的转运蛋白移动未折叠的蛋白质，将它们穿过细胞膜，就像穿过针眼的线一样。相比之下，第二种类型的转运蛋白，我们称之为达特系统，将折叠的蛋白质跨膜移动。这比线程化更具挑战性，因此人们认为达特系统通过一种不寻常的机制运行。达特系统是许多细菌过程所必需的，包括能量产生、细胞分裂、营养获取、致病以及土壤细菌与植物的固氮共生。达特蛋白转运系统不仅存在于细菌中，而且也存在于植物的叶绿体中，在叶绿体中形成和维持进行光合作用所需的蛋白质是必需的。 达特系统是一个可能的药物靶点，因为它是细菌致病所必需的，但在人类或动物中没有发现。它也是生物技术的兴趣，因为它可以用来分泌有用的蛋白质产品。我们最近已经确定了达特蛋白易位装置的核心部分的分子结构。这个项目旨在利用这些结构数据来帮助我们了解达特机器是如何工作的。

Some proteins in bacteria are located outside the membrane that surrounds the cell, for example the toxins produced by bacterial pathogens. Because all proteins are made inside the bacterium the external proteins have to be moved out of the cell across the normally impermeable cell membrane by machines termed protein transporters. One type of transporter moves unfolded proteins, threading them across the membrane like string through the eye of a needle. By contrast, a second type of transporter, which we term the Tat system, moves folded proteins across the membrane. This is much more challenging than threading and so it is thought that the Tat system operates by an unusual mechanism. The Tat system is required for many bacterial processes including energy generation, cell division, nutrient acquisition, pathogenesis, and the nitrogen-fixing symbiosis of soil bacteria with plants. The Tat protein transport system is not only found in bacteria but is also present in the chloroplasts of plants where it is essential to form and maintain the proteins required to carry out photosynthesis. The Tat system is a possible drug target because it is required for bacterial pathogenesis but is not found in humans or animals. It is also of biotechnological interest because it could be utilised to secrete useful protein products. We have recently determined the molecular structure of the core part of the Tat protein translocation apparatus. This project aims to exploit this structural data to help us understand how the Tat machinery works.