Lipid binding attenuates channel closure of the outer membrane protein OmpF

Liko, Idlir, Degiacomi, Matteo T., Lee, Sejeong, Newport, Thomas D., Gault, Joseph, Reading, Eamonn, Hopper, Jonathan T. S., Housden, Nicholas G., White, Paul, Colledge, Matthew, Sula, Altin, Wallace, B. A., Kleanthous, Colin, Stansfeld, Phillip J., Bayley, Hagan, Benesch, Justin L. P., Allison, Timothy M. and Robinson, Carol V. (2018) Lipid binding attenuates channel closure of the outer membrane protein OmpF. Proceedings of the National Academy of Sciences, 115 (26), 6691-6696. (doi:10.1073/pnas.1721152115).

Abstract

Only marginal charge-induceddifferences were observed for inner membrane proteins: theammonia channel (AmtB) or the mechanosensitive channel. Tounderstand these different sensitivities, we performed an exten-sive bioinformatics analysis of membrane protein structures andfound that OmpF, and to a lesser extent FpvA and VDAC, haveatypically high local densities of basic and acidic residues in theirlipid headgroup-binding regions. Coarse-grained molecular dy-namics simulations, in mixed lipid bilayers, further implicatechanges in charge by demonstrating preferential binding ofanionic POPG over zwitterionic POPC to protonated OmpF, aneffect not observed to the same extent for AmtB. Moreover,electrophysiology and mass-spectrometry–based ligand-bindingexperiments, at low pH, show that POPG can maintain OmpF chan-nels in open conformations for extended time periods. Since theouter membrane is composed almost entirely of anionic lipopoly-saccharide, with similar headgroup properties to POPG, such anioniclipid binding could prevent closure of OmpF channels, thereby in-creasing access of antibiotics that use porin-mediated pathways.

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Contributors

Author: Eamonn Reading

Author: Paul White

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