KU Leuven-University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Molecular Bacteriology, B-3000 Leuven, Belgium.
Institute of Molecular Biology and Biotechnology, FORTH and Department of Biology, University of Crete, PO Box 1385, GR-711 10 Iraklio, Crete, Greece.
Nat Microbiol. 2016 Jul 26;1(8):16107. doi: 10.1038/nmicrobiol.2016.107.
While the entire proteome is synthesized on cytoplasmic ribosomes, almost half associates with, localizes in or crosses the bacterial cell envelope. In Escherichia coli a variety of mechanisms are important for taking these polypeptides into or across the plasma membrane, maintaining them in soluble form, trafficking them to their correct cell envelope locations and then folding them into the right structures. The fidelity of these processes must be maintained under various environmental conditions including during stress; if this fails, proteases are called in to degrade mislocalized or aggregated proteins. Various soluble, diffusible chaperones (acting as holdases, foldases or pilotins) and folding catalysts are also utilized to restore proteostasis. These responses can be general, dealing with multiple polypeptides, with functional overlaps and operating within redundant networks. Other chaperones are specialized factors, dealing only with a few exported proteins. Several complex machineries have evolved to deal with binding to, integration in and crossing of the outer membrane. This complex protein network is responsible for fundamental cellular processes such as cell wall biogenesis; cell division; the export, uptake and degradation of molecules; and resistance against exogenous toxic factors. The underlying processes, contributing to our fundamental understanding of proteostasis, are a treasure trove for the development of novel antibiotics, biopharmaceuticals and vaccines.
虽然整个蛋白质组都在细胞质核糖体上合成，但几乎有一半与细菌细胞包膜结合、定位于或穿过细菌细胞包膜。在大肠杆菌中，多种机制对于将这些多肽带入或穿过质膜、保持它们的可溶性形式、将它们运送到正确的细胞包膜位置以及将它们折叠成正确的结构是很重要的。在各种环境条件下，包括在应激期间，这些过程的保真度必须得到维持; 如果失败了，蛋白酶就会被招募来降解定位错误或聚集的蛋白质。各种可溶性、可扩散的伴侣蛋白（作为持留蛋白、折叠酶或导肽）和折叠催化剂也被用来恢复蛋白质稳态。这些反应可以是普遍的，涉及多种多肽，具有功能重叠，并在冗余网络中运行。其他伴侣蛋白是专门的因素，只处理少数几种分泌蛋白。已经进化出几种复杂的机制来处理与外膜的结合、整合和穿越。这个复杂的蛋白质网络负责基本的细胞过程，如细胞壁生物发生; 细胞分裂; 分子的输出、摄取和降解; 以及抵抗外来有毒因素。这些有助于我们对蛋白质稳态基本理解的潜在过程是开发新型抗生素、生物制药和疫苗的宝库。
