Assembly of E.Coli Outer Membrane Proteins

蛋白质折叠和组装是核心的生物过程，必须正确地发生才能 所有活细胞的功能。许多毁灭性的人类疾病，包括神经退行性阿尔茨海默氏症和 Pron病是蛋白质折叠和组装错乱的结果。相对较大的数额 硅藻活性的主要作用是确保蛋白质的正确折叠和组装。在以下情况下 错误折叠，蛋白质被驱动到聚集和降解途径。错误折叠蛋白质的降解 是至关重要的，因为它们可能形成有毒的聚集体，这可能会干扰正常的细胞功能。 最大限度地减少聚集(伴侣和折叠酶)或去除聚集体(蛋白酶)的组装因子 因此是互补的细胞活动，受调节以响应蛋白质折叠状态 牢房。 由于膜蛋白折叠的复杂性，研究膜蛋白的组装一直是一项具有挑战性的任务 行为。然而，最近许多膜蛋白的结构分辨率出现爆炸性增长，包括 这项研究为膜蛋白生物发生领域注入了新的动力。这个 拟议的研究旨在了解一种独特的外膜蛋白的组装 大肠杆菌卷曲，ToiC，它折叠成一个新的三维结构。TolC蛋白进行 几种重要的医学和生理功能，包括抗生素排出和毒素分泌。这 研究将确定和表征有助于TolC组装的基因内和基因外因素 变成由α-螺旋和β-链组成的三聚体桶。这些方面将通过以下方式进行研究 利用遗传、分子和生物化学方法。可获得的数据显示，TolC遵循 与目前研究的其他外膜蛋白不同的组装途径，从而提供了一种 发现管理外膜蛋白靶向和组装的新原理的机会。

Protein folding and assembly are central biological processes that must occur correctly for the proper functioning of all living cells. Many devastating human diseases, including neurodegenerative Alzheimer and Prion diseases, are the consequence of disarrayed protein folding and assembly. A relatively large amount of celtuiar activity is dedicated to ensure the correct folding and assembly of proteins. In the event of misfolding, proteins are driven to aggregation and degradation pathways. Degradation of misfolded proteins is crucial because they may form toxic aggregates, which can interfere with normal cellular functions. Assembly factors that minimize aggregation (chaperones and foldases) or remove aggregates (proteases) are therefore complementary cellular activities that are regulated in response to the protein-folding status of the cell. Studying the assembly of membrane proteins has been a challenging task owing to their complex folding behavior. However, a recent explosion in the structural resolution of many membrane proteins, including those included in this study, has given a renewed impetus to the field of membrane protein biogenesis. The proposed research is directed at understanding the assembly of a unique outer membrane protein of Escherichia coil, ToiC, which folds into a novel three-dimensional structure. The TolC protein carries out several medically and physiologically important functions including antibiotic efflux and toxin secretion. This research will identify and characterize intragenic and extragenic factors that contribute to TolC's assembly into trimeric barrels composed of alpha-helices and beta-strands. These aspects will be studied through exploiting genetic, molecular, and biochemical methods. The available data show that TolC follows an assembly pathway distinct from alt other outer membrane proteins studied so far, thus providing an opportunity to uncover novet principles governing outer membrane protein targeting and assembly.