Plasticity and transient binding are key ingredients of the periplasmic chaperone network.
Open accessAbstract
SurA, Skp, FkpA, and DegP constitute a chaperone network that ensures biogenesis of outer membrane proteins (OMPs) in Gram‐negative bacteria. Both Skp and FkpA are holdases that prevent the self‐aggregation of unfolded OMPs, whereas SurA accelerates folding and DegP is a protease. None of these chaperones is essential, and we address here how functional plasticity is manifested in nine known null strains. Using a comprehensive computational model of this network termed OMPBioM, our results suggest that a threshold level of steady state holdase occupancy by chaperones is required, but the cell is agnostic to the specific holdase molecule fulfilling this function. In addition to its foldase activity, SurA moonlights as a holdase when there is no expression of Skp and FkpA. We further interrogate the importance of chaperone–client complex lifetime by conducting simulations using lifetime values for Skp complexes that range in length by six orders of magnitude. This analysis suggests that transient occupancy of durations much shorter than the Escherichia coli doubling time is required. We suggest that fleeting chaperone occupancy facilitates rapid sampling of the periplasmic conditions, which ensures that the cell can be adept at responding to environmental changes. Finally, we calculated the network effects of adding multivalency by computing populations that include two Skp trimers per unfolded OMP. We observe only modest perturbations to the system. Overall, this quantitative framework of chaperone–protein interactions in the periplasm demonstrates robust plasticity due to its dynamic binding and unbinding behavior.
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The release of the mature domain into the periplasm is likely supported by periplasmic chaperones.
“This latter step is likely supported by periplasmic chaperones (Schäfer et al., 1999; Furst et al., 2018; Chum et al., 2019; Mas et al., 2019) (see below).”
From The Dynamic SecYEG Translocon (2021) · cites this paper as Chum et al., 2019
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Oswald, J., Njenga, R., Natriashvili, A., Sarmah, P., & Koch, H.-G. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.664241 · Cited by 88 · see citing works
- Authors
- Chum, A. P., Shoemaker, S. R., Fleming, P. J., & Fleming, K. G.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Fleming, Karen G.
- Venue
- Protein Science
- Publisher
- Wiley
- Published
- 2019-05-23
- Volume
- 28
- Issue
- 7
- Pages
- 1340-1349
- ISSN
- 0961-8368 (ISSN-L)
- 1469-896X
- PMC
- PMC6566527
- OpenAlex
- W2944015260
- Cited by
- 13
- References
- 34
- Citations by year
- 2024: 3 · 2022: 3 · 2021: 4 · 2020: 3
- FWCI
- 0.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Protein Science (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Directorate for Biological Sciences (MCB1412108)
- National Institute of General Medical Sciences (R01GM079440)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- outer membrane protein biogenesis, SurA, Skp, FkpA, DegP, foldases, functional plasticity, transient binding, multivalency, Escherichia coli, Gram-negative bacteria
- MeSH terms
- Cell Plasticity, Binding Sites, Models, Molecular, Molecular Chaperones, Periplasm, Protein Interaction Mapping
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