Substrate-receptor interactions in the Tat protein transport pathway

Tat 蛋白转运途径中的底物-受体相互作用

• 批准号: MR/K000721/1
• 负责人: Benjamin Berks
• 金额: $ 58.74万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FK000721%2F1
• 关键词: Substrate; receptor; interactions; Tat; protein

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.

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名为蛋白质转运体的机器执行的。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，并最终设计出阻止其工作的新药，该项目将使用尖端技术来阐明运输机制如何识别要运输的蛋白质上的靶向标签。我们还将测试这样一种假设，即TAT转运蛋白是通过在膜上移动标签来工作的，这会将乘客蛋白拉到后面。

项目成果

Precursor-Receptor Interactions in the Twin Arginine Protein Transport Pathway Probed with a New Receptor Complex Preparation.

• DOI: 10.1021/acs.biochem.8b00026
• 发表时间: 2018-03-13
• 期刊: Biochemistry
• 影响因子: 2.9
• 作者: Wojnowska M;Gault J;Yong SC;Robinson CV;Berks BC
• 通讯作者: Berks BC