Review Article

Protein folding in the cell envelope of Escherichia coli

  • Nature Microbiology 1, Article number: 16107 (2016)
  • doi:10.1038/nmicrobiol.2016.107
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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.

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Acknowledgements

We thank K. Fleming and S. Krueger for providing Skp and Skp:OmpA structures; and T. Oas, J. F. Collet, H. Remaut, D. Rapoport and S. White for useful discussions. Our research is funded by grants (to A.E.): KUL-Spa (Onderzoekstoelagen 2013; Bijzonder Onderzoeksfonds; KU Leuven); RiMembR and T3RecS (Vlaanderen Onderzoeksprojecten (FWO)); StrepSynth (FP7 KBBE.2013.3.6-02: Synthetic Biology towards applications; #613877; European Union); DIP-BiD (AKUL/15/40 - G0H2116N; Hercules/FWO) and (to S.K.): G0B4915N; FWO. G.O. is an Onassis Foundation doctoral fellow. J.D.G. is an FWO doctoral fellow. V.Z. is a PDM KU Leuven and Rega foundation postdoctoral fellow.

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Affiliations

  1. KU Leuven—University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Molecular Bacteriology, B-3000 Leuven, Belgium.

    • Jozefien De Geyter
    • , Alexandra Tsirigotaki
    • , Valentina Zorzini
    • , Anastassios Economou
    •  & Spyridoula Karamanou
  2. Institute of Molecular Biology and Biotechnology, FORTH and Department of Biology, University of Crete, PO Box 1385, GR-711 10 Iraklio, Crete, Greece.

    • Georgia Orfanoudaki
    •  & Anastassios Economou

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Contributions

J.D.G. drafted the manuscript and prepared figures; A.T. prepared figures, assembled the table of periplasmic folding mechanisms and contributed to drafting; G.O. retrieved data from databases and performed bioinformatic analyses; V.Z. prepared figures and analysed PDB structures. A.E. and S.K. drafted and edited the manuscript. A.E. and S.K. conceived and guided the project. All authors read and approved the final manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Anastassios Economou or Spyridoula Karamanou.

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    Supplementary Methods, Supplementary Figures 1–5, Supplementary Tables 1 and 2 legends, Supplementary Table 3, Supplementary References

Excel files

  1. 1.

    Supplementary Table 1

    Sequence and structural features of E. coli K12 secretory and cytoplasmic proteins.

  2. 2.

    Supplementary Table 2

    Comparison of SCOP families in the secretome and cytoplasmic proteins.