Machin, J.M., Ranson, N.A. and Radford, S. E. orcid.org/0000-0002-3079-8039 (Accepted: 2025) OmpA specifically modulates the activity of enzymes that reside in the crowded bacterial outer membrane. Journal of Molecular Biology. ISSN 0022-2836 (In Press)
Abstract
The outer membrane (OM) of lipopolysaccharide (LPS) containing-diderm bacteria is crowded with outer membrane proteins (OMPs) that reside in a membrane that is relatively rich in protein and poor in lipid. As a consequence, extensive interactions between OMPs occur. Yet, how these interactions affect OMP function remains unexplored. Here, we examine the effect of OmpA on the activity of three different OMP enzymes, OmpLA (a phospholipase), PagP (a palmitoyltransferase) and OmpT (a protease). We show that OmpA-OmpT interactions enhance the activity of OmpT, and that this catalytic enhancement is mediated via their extracellular loops, an effect that is not observed with other common OMPs, including OmpF and OmpX. In contrast, OmpA specifically reduces the activity of PagP, while OmpLA activity shows no significant change. Possible interactions between the abundant E. coli OMPs (OmpA, OmpF/C, OmpT, OmpX, MipA) and all other E. coli OMPs were screened via Alphafold predictions, with the results suggesting that smaller OMPs are generally more promiscuous interactors, and identifying new interactions that may plausibly form in the OMP-rich islands in the OM. Together, the results identify a previously underappreciated role for specific OMPOMP interactions in modulating protein function in the OM, and highlight how evolution may have exploited the high local concentrations of abundant OMPs in the OM to tune enzyme activity.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | This is an author produced version of an article accepted for publication in the Journal of Molecular Biology (JMB), made available under the terms of the Creative Commons Attribution License (CC-BY), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | Outer membrane protein (OMP), OMP-OMP interactions, OMP islands, Bacterial outer membrane |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) |
Funding Information: | Funder Grant number Royal Society RSRP\R1\211057 |
Depositing User: | Symplectic Publications |
Date Deposited: | 14 Jul 2025 07:24 |
Last Modified: | 14 Jul 2025 07:50 |
Status: | In Press |
Publisher: | Elsevier |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:229036 |