Protein folding in the cell envelope of Escherichia coli

Abstract

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.

Identification of specific posttranslational O -mycoloylations mediating protein targeting to the mycomembrane

“…Additionally, an outermost layer may exist in some suborder (17,18). The biogenesis and the organization of the Corynebacteriales mycomembrane are far less documented than for the LPScontaining counterpart from Gram-negative outer membranes (19)(20)(21). Notably, very few mycomembrane proteins have been structurally and functionally characterized (10,22), and secretion pathways resulting in mycomembrane association remained an enigma.…”

Identification of a Large Family of Slam-Dependent Surface Lipoproteins in Gram-Negative Bacteria

“…However, this creates a logistic challenge for the transport of various biomolecules to and from the extracellular milieu and across the outer membrane of the bacteria (Pagès et al, 2008; Delcour, 2009). Toward this end, Gram-negative bacteria have developed dedicated translocation systems that deliver various families of proteins and other biomolecules across the outer membrane (Nikaido, 2003; Costa et al, 2015; Geyter et al, 2016). The mechanism for this transport is distinct from translocation systems found in the inner membrane owing to the lack of ATP in the periplasm and is an active field of research (Karuppiah et al, 2011).…”

The β-barrel assembly machinery in motion

“…The chaperone SurA has been implicated to be the key chaperone during targeting of OMPs ; however, Skp has also been shown to have a role during chaperone-mediated biogenesis for some OMPs, even rescuing ‘off-pathway’ OMPs that are usually chaperoned by SurA 13 . However, recent studies indicate a more complicated pathway where OMPs may experience complex chaperone networks that are driven by energy landscapes within the periplasm 14–16 . Misfolded OMPs that cannot be rescued are degraded by the periplasmic protease DegP to prevent their accumulation and thus cellular toxicity 13, 17–19 .…”