Understanding the role of the Bam complex in the biogenesis of outer membrane proteins
Understanding the role of the Bam complex in the biogenesis of outer membrane proteins
批准号:
G0801209/1
负责人:
Ian Henderson
金额:
$52.56万
依托单位:
依托单位国家:
英国
项目类别:
Research Grant
财政年份:
2009
资助国家:
英国
项目状态:
已结题
起止时间:
2009 至 --
中文摘要
细菌种类可分为两个基本组:革兰氏阳性和革兰氏阴性。这两组之间的主要区别是每个人拥有的细胞膜的数量。因此,革兰氏阳性细菌具有一种称为细胞质膜的膜,革兰氏阴性细菌具有两种称为内膜和外膜的膜。革兰氏阳性菌的细胞质膜和革兰氏阴性菌的内膜具有许多相同的特征,并且以大致相同的方式发挥功能。在革兰氏阴性菌的情况下,外膜通过提供对无数抗菌剂的保护而对生存至关重要。然而,外膜的存在也给细菌带来了问题;细菌产生的有毒物质必须穿过外膜运输出细胞,营养物质必须从细胞外收获并穿过外膜运输到细胞中。此外,细菌在特定环境中的存活通常需要产生插入细胞膜并分泌到细胞外的蛋白质。这些因素使得复杂的生物机器的发展成为必要,这些机器可以组装外膜的组件并将蛋白质分泌到细胞外。最近发现的这种组装机器的一个组件是一种名为Omp 85的蛋白质。这种蛋白存在于所有革兰氏阴性菌中,是细菌生存所必需的。有趣的是,这种蛋白质也存在于线粒体中。这些微小的器官为人类、动物和植物细胞提供能量;没有Omp 85蛋白,线粒体就无法发挥功能,细胞也无法生存。此外,这种蛋白质也存在于叶绿体中;叶绿体是植物细胞的微小器官,可以使植物将二氧化碳转化为氧气; Omp 85也是叶绿体生存所必需的。Omp 85同源物代表了药物的基本和重要靶标。由于Omp 85在所有革兰氏阴性细菌物种中是保守的,因此可以设计策略来抑制Omp 85的功能,从而阻断许多疾病的发病机制。然而,由于对Omp 85如何发挥作用的了解很少,这种治疗潜力无法有效地解锁或开发。该项目旨在通过使用包括基因突变和生物化学在内的各种技术来研究这种蛋白质的功能。
英文摘要
Bacterial species can be divided into two basics groups: Gram-positive and Gram-negative. The major difference between these two groups is the number of cell membranes that each possesses. Thus, Gram-positive bacteria possess one membrane called the cytoplasmic membrane and Gram-negative bacteria possess two called the inner membrane and the outer membrane. The cytoplasmic membrane of Gram-positive bacteria and the inner membrane of Gram-negative bacteria share many of the same features and function in much the same way. In the case of Gram-negative bacteria the outer membrane is essential for survival by providing protection against a myriad of antibacterial agents. However, the presence of the outer membrane also poses problems for the bacterium; toxic substances produced by the bacterium have to be transported across the outer membrane out of the cell and nutrients have to be harvested from outside the cell and transported across the outer membrane into the cell. Additionally, survival of bacteria within a particular environment often requires the production of proteins which are inserted into the membrane and secreted outside the cell. These factors have necessitated the development of sophisticated biological machines to assemble components of the outer membrane and to secrete proteins outside the cell.One component of this assembly machinery that was recently discovered is a protein termed Omp85. This protein is found in all Gram-negative bacteria and is essential for bacterial survival. Interestingly, this protein is also found in mitochondria. These are minute organs that supply energy to human, animal and plant cells; without the Omp85 protein the mitochondria cannot function and the cells cannot survive. In addition, this protein is also found in chloroplasts; the minute organs of plants cells than allow plants to convert carbon dioxide to oxygen; Omp85 is also essential for survival of chloroplasts.The Omp85 homologues represent a fundamentally and important target for drugs. Since Omp85 is conserved in all Gram-negative bacterial species it may be possible to design strategies to inhibit the function of Omp85 and thus block pathogenesis of many diseases. However, with little understanding of how Omp85 functions this therapeutic potential cannot be effectively unlocked or exploited. This project aims to investigate how this protein functions by using a variety of techniques including genetic mutations and biochemistry.
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