ArticleBiophysical journal2021
Lpp positions peptidoglycan at the AcrA-TolC interface in the AcrAB-TolC multidrug efflux pump.
Article in Biophysical journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- A lipoprotein partner for theeLife · 2026Article
- MemPrO: A Predictive Tool for Membrane Protein Orientation.Journal of chemical theory and computation · 2026Article
- Impact of exporter proteins and their engineering on the productivity of Corynebacterium.Applied microbiology and biotechnology · 2025Review
- Unveiling the impact ofInfection and immunity · 2024Article
- Seeing is believing: Illuminating the Gram-negative outer membrane with molecular dynamics simulations.Current opinion in structural biology · 2024Review
- Thicket and Mesh: How the Outer Membrane Can Resist Tension Imposed by the Cell Wall.The journal of physical chemistry. B · 2024Article
- Recent Advances in Modeling Membrane β-Barrel Proteins Using Molecular Dynamics Simulations: From Their Lipid Environments to Their Assemblies.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Structures and Efflux Mechanisms of the AcrAB-TolC Pump.Sub-cellular biochemistry · 2024Article
- Molecular Modeling and Simulation of the Mycobacterial Cell Envelope: From Individual Components to Cell Envelope Assemblies.The journal of physical chemistry. B · 2023Review
- New understanding of multidrug efflux and permeation in antibiotic resistance, persistence, and heteroresistance.Annals of the New York Academy of Sciences · 2023Review
- Conformational dynamics and putative substrate extrusion pathways of the N-glycosylated outer membrane factor CmeC from Campylobacter jejuni.PLoS computational biology · 2023Article
- A Defect in Lipoprotein Modification by Lgt Leads to Abnormal Morphology and Cell Death in Escherichia coli That Is Independent of Major Lipoprotein Lpp.Journal of bacteriology · 2022Article
- Weaving of bacterial cellulose by the Bcs secretion systems.FEMS microbiology reviews · 2022Review
- What have molecular simulations contributed to understanding of Gram-negative bacterial cell envelopes?Microbiology (Reading, England) · 2022Review
- Article
- A Model for Allosteric Communication in Drug Transport by the AcrAB-TolC Tripartite Efflux Pump.Antibiotics (Basel, Switzerland) · 2022Article
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
The multidrug efflux pumps of Gram-negative bacteria are a class of complexes that span the periplasm, coupling both the inner and outer membranes to expel toxic molecules. The best-characterized example of these tripartite pumps is the AcrAB-TolC complex of Escherichia coli. However, how the complex interacts with the peptidoglycan (PG) cell wall, which is anchored to the outer membrane (OM) by Braun's lipoprotein (Lpp), is still largely unknown. In this work, we present molecular dynamics simulations of a complete, atomistic model of the AcrAB-TolC complex with the inner membrane, OM, and PG layers all present. We find that the PG localizes to the junction of AcrA and TolC, in agreement with recent cryo-tomography data. Free-energy calculations reveal that the positioning of PG is determined by the length and conformation of multiple Lpp copies anchoring it to the OM. The distance between the PG and OM measured in cryo-electron microscopy images of wild-type E. coli also agrees with the simulation-derived spacing. Sequence analysis of AcrA suggests a conserved role for interactions with PG in the assembly and stabilization of efflux pumps, one that may extend to other trans-envelope complexes as well.
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