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Lipid binding attenuates channel closure of the outer membrane protein OmpF

Lipid binding attenuates channel closure of the outer membrane protein OmpF
Lipid binding attenuates channel closure of the outer membrane protein OmpF
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.
0027-8424
6691-6696
Liko, Idlir
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Degiacomi, Matteo T.
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Lee, Sejeong
7b8ab165-fc9d-4ec0-ba26-deab261d3f74
Newport, Thomas D.
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Gault, Joseph
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Reading, Eamonn
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Hopper, Jonathan T. S.
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Housden, Nicholas G.
d2ad0930-bb93-4e13-a967-4ecdc84a48e4
White, Paul
2dd2477b-5aa9-42e2-9d19-0806d994eaba
Colledge, Matthew
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Sula, Altin
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Wallace, B. A.
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Kleanthous, Colin
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Stansfeld, Phillip J.
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Bayley, Hagan
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Benesch, Justin L. P.
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Allison, Timothy M.
422ca820-8726-41a0-b6d3-2be84e79a7e4
Robinson, Carol V.
54050df3-1bf7-42d9-a5eb-c39e010f1bbe
Liko, Idlir
10e8e8d2-fde8-42b7-8e05-ad18e9997323
Degiacomi, Matteo T.
b15ad963-4479-49e8-8be1-e41cdc1908aa
Lee, Sejeong
7b8ab165-fc9d-4ec0-ba26-deab261d3f74
Newport, Thomas D.
1c70a26d-cf62-44e1-886c-fcfb8495f223
Gault, Joseph
c15d2b21-defd-4c42-bf46-2dfca93535d6
Reading, Eamonn
62fed933-f867-4c72-89e7-83aea573a836
Hopper, Jonathan T. S.
986f2749-1e39-48ea-aed7-470146dffe80
Housden, Nicholas G.
d2ad0930-bb93-4e13-a967-4ecdc84a48e4
White, Paul
2dd2477b-5aa9-42e2-9d19-0806d994eaba
Colledge, Matthew
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Sula, Altin
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Wallace, B. A.
3f88e2ca-2b6a-48ab-8dfc-436d95c6d61b
Kleanthous, Colin
3d6d354c-bddf-4b64-8e4a-3f5b523802c2
Stansfeld, Phillip J.
b49798a7-ce8f-4288-a4b8-d78c48445957
Bayley, Hagan
929363fb-8539-43de-9d86-153ceb26e03e
Benesch, Justin L. P.
9bdc06a0-68d0-48f0-89d3-fd5baff7168b
Allison, Timothy M.
422ca820-8726-41a0-b6d3-2be84e79a7e4
Robinson, Carol V.
54050df3-1bf7-42d9-a5eb-c39e010f1bbe

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).

Record type: Article

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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More information

Accepted/In Press date: 30 April 2018
e-pub ahead of print date: 11 June 2018

Identifiers

Local EPrints ID: 479144
URI: http://eprints.soton.ac.uk/id/eprint/479144
ISSN: 0027-8424
PURE UUID: d47f012b-2a03-42cf-b7ac-2a0a4c7b4402
ORCID for Eamonn Reading: ORCID iD orcid.org/0000-0001-8219-0052
ORCID for Paul White: ORCID iD orcid.org/0000-0002-4787-8713

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Date deposited: 20 Jul 2023 16:37
Last modified: 11 Jul 2024 02:14

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Contributors

Author: Idlir Liko
Author: Matteo T. Degiacomi
Author: Sejeong Lee
Author: Thomas D. Newport
Author: Joseph Gault
Author: Eamonn Reading ORCID iD
Author: Jonathan T. S. Hopper
Author: Nicholas G. Housden
Author: Paul White ORCID iD
Author: Matthew Colledge
Author: Altin Sula
Author: B. A. Wallace
Author: Colin Kleanthous
Author: Phillip J. Stansfeld
Author: Hagan Bayley
Author: Justin L. P. Benesch
Author: Timothy M. Allison
Author: Carol V. Robinson

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