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Cited by 3Antibiotic Resistance in BacteriaBacterial Genetics and BiotechnologyDrug Transport and Resistance Mechanisms

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A lipoprotein partner for the Escherichia coli outer membrane protein TolC

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Horne, Jim, Kaplan, Elise, Jin, Ben, Abbott, Kieran, Flores, Victor, Petsolari, Emmanouela, Gradon, Jan, Ntsogo, Yvette, Harris, Andrzej, Yu, Dingquan, Zarkan, Ashraf, Luisi, Ben F·2026·eLife
DOI 10.7554/elife.110666.3

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Abstract

The outer membrane protein TolC from Escherichia coli belongs to an extensive superfamily whose members are found throughout the didermal, Gram-negative bacterial lineages. The protein serves as an activated exit duct in multi-drug efflux pumps and protein secretion machinery. Many TolC homologues bear a lipid modification on the N-terminus that embeds into the inner leaflet of the outer membrane and appears to have been a conserved feature; however, the moiety is absent entirely in the E. coli TolC. We have discovered that the E. coli lipoprotein YbjP interacts extensively with the periplasmic surface of TolC and its N-terminal lipid moiety is embedded in the membrane, mimicking the intramolecular and modification-membrane interactions seen in TolC homologues. Here, we present cryo-EM structures of the MacA-MacB-TolC and AcrA-AcrB-TolC tripartite pumps complexed to YbjP. Although the association occurs spontaneously both in vitro and in vivo, the YbjP-TolC interaction is not required for efflux activity under standard laboratory conditions. YbjP may contribute to stabilising the orientation and distribution of TolC in the outer membrane, as well as the expression of transporters for tryptophan and cyclic peptide toxins.

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Metadata

Authors
Horne, J., Kaplan, E., Jin, B., Abbott, K., Flores, V., Petsolari, E., Gradon, J., Ntsogo, Y., Harris, A., Yu, D., Zarkan, A., & Luisi, B. F.
Affiliations
  • University of Cambridge (GB)
  • Department of Biochemistry, University of Cambridge
Corresponding author
Luisi, Ben F
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2026-04-15
Volume
15
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.110666.3
OpenAlex
W4408706463
Cited by
3
References
2
Citations by year
2026: 1
FWCI
2.22
Type
journal article
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • HAL (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
Funders
  • Wellcome Trust (10.35802/222451)
  • European Research Council (742210)
  • School of the Biological Sciences, University of Cambridge (Transition to Independence)
  • Rosetrees Trust (JS16/TT12021\1)
  • Isaac Newton Trust (21.22(a)iii)
Topics
  • Health Sciences › Medicine › Microbiology (medical) › Antibiotic Resistance in Bacteria
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Keywords
TolC, lipoproteins, Escherichia coli, outer membrane proteins, tripartite efflux pump, AcrAB-TolC, protein secretion, cryo-EM structure, tryptophan transport, cyclic peptide toxins

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