Structural & Biochemical Characterisation of the Streptococcus pneumoniae Early-Stage Division Complex, FtsEX-PcsB.

结构性

• 批准号: 2264827
• 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: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2264827
• 关键词: Structural; Biochemical; Characterisation; Streptococcus; pneumoniae

Bacterial cell division is seen as one of the most highly conserved processes that occurs in that kingdom. FtsA (bacterial actin) works to anchor the Z-ring of FtsZ (bacterial tubulin) to the inner side of the cytoplasmic membrane, before other downstream components of the Divisome assemble in a highly coordinated manner. Two of these proteins are the ATPase FtsE, and the polytopic membrane protein FtsX that assemble as part of the early-stage Divisome assembly, which are required for subsequent assembly of further downstream components. Further to this, the FtsEX complex has been implemented in a peptidoglycan (PG) breakdown during daughter cell separation. To facilitate this, FtsX associates with the probable PG hydrolase, PcsB. These interaction as well as the control mechanisms are not well understood, and may provide crucial insight into future chemotherapeutic strategies that will govern the development of next-generation antibiotics. We propose to study this system in the Gram-positive organism, Streptococcus pneumoniae; an opportunistic pathogen responsible for around 6000 deaths per year, predominantly in the elderly and children under 5. Recently, the S. pneumoniae PcsB crystal structure has been solved, revealing a V-shaped conformation, the active site containing CHAPS domain residing close to the coiled-coil domain. Based on the homologous interaction between FtsX and EnvC in E. coli, PcsB will need to undergo a conformational change in order to become activated. This may be facilitated by the ATPase action of FtsE, though the molecular mechanisms are unclear; which is in part what we propose to study in this project.

细菌细胞分裂被视为该王国中发生的最高度保守的过程之一。 FTSA（细菌肌动蛋白）致力于将FTSZ（细菌小管蛋白）的Z环锚定在细胞质膜的内侧，然后以高度协调的方式组装了分裂体的其他下游成分。这些蛋白质中的两种是ATPase FTSE，并且是作为早期分裂组组件的一部分组装的聚膜蛋白FTSX，这是随后组装进一步下游成分所必需的。除此之外，在子细胞分离过程中，FTSEX复合物已在肽聚糖（PG）分解中实现。为了促进这一点，FTSX与可能的PG水解酶PCSB相关联。这些相互作用以及控制机制尚不清楚，并且可能会为未来的化学治疗策略提供至关重要的见解，从而控制下一代抗生素的发展。我们建议在革兰氏阳性生物体肺炎链球菌中研究该系统。一个机会性病原体每年约6000例死亡，主要是老年人和5岁以下的儿童。最近，已解决了肺炎链球菌PCSB晶体结构，揭示了V形构象，该构象具有坐落在附近的固定组合域附近的活动部位，其中包含CHAPS域。基于大肠杆菌中FTSX和ENVC之间的同源相互作用，PCSB将需要经历构象变化才能被激活。尽管分子机制尚不清楚，但FTSE的ATPase作用可能会促进。这部分是我们建议在该项目中研究的内容。