The multifunctional role of MraY in bacterial cell wall biogenesis

MraY 在细菌细胞壁生物发生中的多功能作用

• 批准号: 2596908
• 金额: --
• 依托单位: University of Warwick
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2596908
• 关键词: multifunctional; role; MraY; bacterial; cell

Bacteria have developed multiple barriers to protect themselves from attack by our immune system, antibiotics and external threat. As a bacterium grows and divides it requires a variety of pathways to transport and assemble this outer casing. Many of the building-blocks for constructing the outer cell surface are attached to a lipid carrier molecule, called a polyprenyl or C55P, for transport. Central to this study is determining how the C55P carrier molecule is then recycled to the cell interior for transport of further cell surface constituents. There are multiple candidate pathways for transport of the C55P carrier molecule back into the cell, but the precise molecular details of transport are still to be determined. As part of this study we will characterise the route for C55P recycling and hypothesise how this process may be inhibited. Our current hypothesis is that a protein, called MraY, is one of the candidates to fulfil this process, and therefore we would like to test this hypothesis with both computational and experimental biochemical methods. We will also contextualise this process, by showing the interactions made by the MraY protein and other components involved in cell wall biogenesis, including the cytoskeletal protein, MreB.We will apply our computational methods to breathe life into the static protein structures by permitting dynamic changes and also modelling the surrounding biological environment. We will use these methods to devise further hypotheses to test experimentally through biochemical approaches and microbiology assays.Knowledge of these interactions are important from the perspective of inhibiting these process through the development of novel antibiotics. By better understanding the precise details of these molecular systems, we can strategically design novel drug inhibitors and therefore developing innovative antibiotics that will enable us to treat otherwise drug-resistant infections.

细菌已经形成了多种屏障，以保护自己免受我们的免疫系统，抗生素和外部威胁的攻击。随着细菌的生长和分裂，它需要多种途径来运输和组装这种外壳。许多用于构建细胞外表面的构建块附着在称为聚异戊二烯或C55P的脂质载体分子上，用于运输。这项研究的核心是确定C55 P载体分子如何再循环到细胞内部，以运输更多的细胞表面成分。有多种候选途径将C55 P载体分子转运回细胞，但转运的精确分子细节仍有待确定。作为本研究的一部分，我们将研究C55P再循环的途径，并假设如何抑制这一过程。我们目前的假设是，一种名为MraY的蛋白质是完成这一过程的候选者之一，因此我们想用计算和实验生化方法来验证这一假设。我们还将通过展示MraY蛋白和参与细胞壁生物发生的其他成分（包括细胞骨架蛋白MreB）之间的相互作用，将这一过程置于背景中。我们将应用我们的计算方法，通过允许动态变化为静态蛋白质结构注入活力，并对周围的生物环境进行建模。我们将使用这些方法来设计进一步的假设，通过生物化学方法和微生物测定进行实验测试。从通过开发新型抗生素来抑制这些过程的角度来看，了解这些相互作用是很重要的。通过更好地了解这些分子系统的精确细节，我们可以战略性地设计新型药物抑制剂，从而开发创新的抗生素，使我们能够治疗耐药感染。