biostudies-literatureMachin JMJohns Hopkins UniversityUniversity of WashingtonUK Research and Innovation Medical Research CouncilThe Royal SocietyWellcome Trust169346https://www.ebi.ac.uk/biostudies/studies/S-EPMC7617971biostudies-literatureUnknown437(19)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 activJournal of molecular biologyOmpA Specifically Modulates the Activity of Enzymes that Reside in the Crowded Bacterial Outer Membrane.PMC7617971MR/Y012453/1RSRP\\R1\\211057222373/Z/21/ZRadford SEMachin JMRanson NAfalseOmpA Specifically Modulates the Activity of Enzymes that Reside in the Crowded Bacterial Outer Membrane.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 activ2025-01-01T00:00:00Z2025 Jul2026-03-27T15:56:49.428Z2025-08-27T03:07:55.357ZS-EPMC76179714066959210.1016/j.jmb.2025.169346