TARGETING AND ASSEMBLY OF E COLI OUTER MEMBRANE PROTEINS

描述：蛋白质的靶向和组装是基本的 生物过程。在许多情况下，目标信号由下式定义 序列的小衬里延伸，例如存在于氨基上的那些 细菌和真核生物中分泌蛋白质的末端。而这些 大肠杆菌中的序列帮助蛋白质离开细胞质，它们 不确定分泌蛋白在体内的最终位置 胞外室：周质和外膜。 这个项目的结果强调了这样一种观点，即目标信号 因为外膜蛋白驻留在部分折叠的 中间体。这些中间体的折叠状态受 分子的本征性质及其与其他分子的相互作用 细胞成分包括伴侣蛋白和脂多糖， 它只定位在外膜上。新基因 本项目中概述的方法将有助于揭示 基因内信息，并提供更好的动态理解 靶向和定位过程中不同细胞成分之间的相互作用 外膜蛋白的组装。因为脂类之间的相互作用 成分和蛋白质存在于所有生物膜中，结果 应该有广泛的普遍利益。 OmpF、OMPC和Lamb将被用作模型蛋白。这些蛋白质作为 噬菌体的受体，形成允许扩散的通道 水溶性的溶质。OmpF和Lamb的三维结构 已经得到了解决，同时允许更好地理解 这些蛋白质的结构-功能关系，几乎没有阐明如何 他们到达了目的地。 这个项目的长期目标是了解生物的发生 外膜蛋白和外膜的分子结构。 这些目标将通过基因的应用来实现 可行并已取得重要成果和新成果的方法 洞察力。

DESCRIPTION: The targeting and assembly of proteins are fundamental biological processes. In many instances, the targeting signal is defined by small liner stretches of sequence such as those present at the amino terminal end of secreted proteins in bacteria and eukaryotes. While these sequences in Escherichia coli assist proteins in exiting the cytoplasm, they do not determine the final location of secreted proteins within the extracytoplasmic compartments: periplasm and outer membrane. Results from this project have emphasized the view that the targeting signal for outer membrane proteins resides within the partially folded intermediates. The folding states of these intermediates are guided by the intrinsic properties of the molecule and its interactions with other cellular components including chaperone proteins and lipopolysaccharide, which is exclusively localized in the outer membrane. Novel genetic approaches outlined in this project will assist in revealing the nature of intragenic information and provide a better understanding of the dynamic interactions between various cellular components during the targeting and assembly of outer membrane proteins. Because interactions between lipidic components and proteins occur in all biological membranes, the results should have broad general interest. OmpF, OmpC and LamB will be used as model proteins. These proteins serve as the receptor for bacteriophages and form channels that allow the diffusion of water soluble solutes. Three-dimensional structures of OmpF and LamB have been resolved which, while permitting a better understanding of the structure-function relationship of these proteins, shed little light on how they reach their destination. The long term goals of this project are to understand the biogenesis of outer membrane proteins and molecular architecture of the outer membrane. These objectives will be achieved through the application of genetic approaches that are feasible and have already yielded important and new insights.