Characterisation of the function and mechanism of a binding-protein dependent secondary transporter

结合蛋白依赖性二级转运蛋白的功能和机制的表征

• 批准号: BB/F014759/1
• 负责人: Gavin Thomas
• 金额: $ 47.75万
• 依托单位: University of York
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FF014759%2F1
• 关键词: Characterisation; function; mechanism; binding; protein

Many bacteria rely almost completely on being able to acquire nutrients from their environment and in bacteria that can only live inside our bodies these chemicals often come from us. One bacterium, Haemophilus influenzae, uses a chemical called sialic acid as a nutrient but also covers its surface in this molecule allowing it to become invisible to components of our immune system. This bacterium is able to acquire the sialic acid using a particular collection of proteins in its membrane called a TRAP transporter. This project aims to study in detail the TRAP transporter that is essential for sialic acid uptake by H. influenzae. If we can determine exactly how this transporter works, we have a better chance at being able to develop novel antimicrobials against this bacterium as we have already demonstrated that if this system is inactive then H. influenzae cannot causes disease. In addition, this TRAP transporter is very amenable to study in the laboratory and we wish to use this particular system to learn a lot of general things about how these transporters work. They are not just limited to functioning in sialic acid uptake, but different TRAP transporters have evolved to transport a wide range of compounds and are present in a wide range of environment, for example, many bacteria that live in the sea (in salty environments) appears to have many TRAP transporters. One of the objectives of this project to try and find out if the presence of salt (sodium) is important for the mechanism of TRAP transporters, which would correlate with them being used preferentially by marine organisms. The results of the project will tell us much more about how one human pathogen is able to capture sialic acid, but also the basic mechanims used by thousands of other bacteria to capture chemicals from the environment using TRAP transporters.

许多细菌几乎完全依赖于能够从环境中获得营养，而在只能生活在我们体内的细菌中，这些化学物质通常来自我们。一种细菌，流感嗜血杆菌，使用一种叫做唾液酸的化学物质作为营养物质，但也用这种分子覆盖其表面，使其对我们的免疫系统成分不可见。这种细菌能够利用其膜上称为TRAP转运蛋白的特定蛋白质集合来获得唾液酸。本项目旨在详细研究H.流感。如果我们能确切地确定这种转运蛋白是如何工作的，我们就有更好的机会开发出针对这种细菌的新型抗菌剂，因为我们已经证明，如果这种系统是无活性的，那么H。流感不会引起疾病。此外，这种TRAP转运蛋白非常适合在实验室中进行研究，我们希望使用这种特殊的系统来了解这些转运蛋白如何工作的一般情况。它们不仅限于在唾液酸摄取中发挥作用，而且不同的TRAP转运蛋白已经进化为运输各种化合物，并且存在于各种环境中，例如，许多生活在海洋中的细菌（在盐环境中）似乎具有许多TRAP转运蛋白。该项目的目标之一是试图找出盐（钠）的存在是否对TRAP转运蛋白的机制很重要，这与海洋生物优先使用它们有关。该项目的结果将告诉我们更多关于一种人类病原体如何捕获唾液酸的信息，以及数千种其他细菌使用TRAP转运蛋白从环境中捕获化学物质的基本机制。

项目成果

Characterization of the l-arabinofuranose-specific GafABCD ABC transporter essential for l-arabinose-dependent growth of the lignocellulose-degrading bacterium Shewanella sp. ANA-3.

L-阿拉伯呋喃糖特异性GAFABCD ABC转运蛋白的表征对于木质纤维素降解细菌SHEWANELLA SP的L-阿拉伯糖依赖性生长必不可少的表征。 ana-3。

• DOI: 10.1099/mic.0.001308
• 发表时间: 2023-03
• 期刊: MICROBIOLOGY-SGM
• 影响因子: 2.8
• 作者: Drousiotis, Konstantinos;Herman, Reyme;Hawkhead, Judith;Leech, Andrew;Wilkinson, Anthony;Thomas, Gavin H
• 通讯作者: Thomas, Gavin H

Structural and mechanistic analysis of a tripartite ATP-independent periplasmic TRAP transporter.

• DOI: 10.1038/s41467-022-31907-y
• 发表时间: 2022-08-04
• 期刊: Nature communications
• 影响因子: 16.6

Tripartite ATP-independent Periplasmic (TRAP) Transporters Use an Arginine-mediated Selectivity Filter for High Affinity Substrate Binding.

• DOI: 10.1074/jbc.m115.656603
• 发表时间: 2015-11-06
• 期刊: The Journal of biological chemistry
• 作者: Fischer M;Hopkins AP;Severi E;Hawkhead J;Bawdon D;Watts AG;Hubbard RE;Thomas GH
• 通讯作者: Thomas GH