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Lipopolysaccharide translocation across the Gram-negative inner membrane; development and exploitation of reagents and knowledge to guide early stage

脂多糖跨革兰氏阴性内膜易位；

基本信息

批准号：
1653926
负责人：
金额：
--
依托单位：
University of Dundee
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2015
资助国家：
英国
起止时间：
2015 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=studentship-1653926
关键词：
Lipopolysaccharide translocation across Gram negative

项目摘要

Lipopolysaccharide (LPS) is a key component of the highly protective cell surface of Gram-negative pathogens. LPS is produced and displayed on the cell surface by the actions of a series of enzymes and a multi-protein transport system termed the Lpt complex. Bacterial survival is compromised if LPS production is curtailed and genetic studies reveal that many of the genes encoding proteins involved in LPS production/transport are essential. A high level of research activity has concentrated on characterisation of the cytosolic biosynthetic enzymes and the proteins that involve transfer from periplasm to cell surface, at the outer membrane. Our plan is to focus on the missing area, and to characterise those proteins involved in the transfer of components across the inner membrane. The three key proteins to be investigated are MsbA, LptF and LptG. MsbA is an ATPase driven flippase, which acts in conjunction with thepotentially heterodimeric LptF-LptG pair. It is an ATP-binding cassette transporter and the fold is known. However, for LptF-G there is are no known orthologous structures. The LptF and LptG proteins typically share about 20% sequence identity and secondary structure predictions suggest a common fold, predicted to comprise 6 transmembrane helices, is present. These two proteins may form homo or heterodimers, a feature we aim to clarify at the onset of the project.

脂多糖（LPS）是革兰氏阴性病原体的高度保护性细胞表面的关键组分。LPS通过一系列酶和称为Lpt复合物的多蛋白转运系统的作用产生并展示在细胞表面上。如果LPS的产生减少，细菌的存活就会受到影响，遗传研究表明，许多编码参与LPS产生/转运的蛋白质的基因是必不可少的。高水平的研究活动集中在表征的胞质生物合成酶和蛋白质，涉及从周质转移到细胞表面，在外膜。我们的计划是集中在缺失的区域，并重新定位那些参与跨内膜成分转移的蛋白质。待研究的三种关键蛋白是MsbA、LptF和LptG。MsbA是一种ATP酶驱动的翻转酶，它与潜在的异源二聚体LptF-LptG对一起起作用。它是一种ATP结合盒转运蛋白，折叠是已知的。然而，对于LptF-G，没有已知的邻位结构。LptF和LptG蛋白通常具有约20%的序列同一性，并且二级结构预测表明存在预测为包含6个跨膜螺旋的共同折叠。这两种蛋白质可能形成同源或异源二聚体，我们的目标是在项目开始时澄清这一特征。