Evidence map›Paper›PMID 34411576›Full record

ArticleBiophysical journal2021

Lpp positions peptidoglycan at the AcrA-TolC interface in the AcrAB-TolC multidrug efflux pump.

James C Gumbart, Josie L Ferreira, Hyea Hwang, Anthony J Hazel, Connor J Cooper, Jerry M Parks, Jeremy C Smith, Helen I Zgurskaya, Morgan Beeby

Open access · greenAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.4field-weighted citation impact, top 20% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 24 citations in OpenAlex.

  1. Article
  2. MemPrO: A Predictive Tool for Membrane Protein Orientation.Journal of chemical theory and computation · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 5 institutions in 2 countries.

James C GumbartSchool of Physics, Georgia Institute of Technology, Atlanta, Georgia. Electronic address: gumbart@physics.gatech.edu.
Josie L FerreiraDepartment of Life Sciences, Imperial College London, London, United Kingdom.
Hyea HwangSchool of Materials Science and Engineering, Georgia Institute of Technology, Atlanta, Georgia.
Anthony J HazelSchool of Physics, Georgia Institute of Technology, Atlanta, Georgia.
Connor J CooperUT/ORNL Center for Molecular Biophysics, Biosciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee.
Jerry M ParksUT/ORNL Center for Molecular Biophysics, Biosciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee.
Jeremy C SmithUT/ORNL Center for Molecular Biophysics, Biosciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee; Department of Biochemistry & Cellular and Molecular Biology, University of Tennessee, Knoxville, Tennessee.
Helen I ZgurskayaDepartment of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma.
Morgan BeebyDepartment of Life Sciences, Imperial College London, London, United Kingdom.
Georgia Institute of Technology · USImperial College London · GBOak Ridge National Laboratory · USUniversity of Oklahoma · USUniversity of Tennessee at Knoxville · US

Funding

Transport across two membranes by AcrAB-TolC complexR01AI052293 · NIAID · UNIVERSITY OF OKLAHOMA NORMAN · PI ZGURSKAYA, HELEN I · 2003 to 2024
$7.7M
Medical Research Council MR/P019374/1Medical Research Council MR/V000799/1NIAID NIH HHS R01 AI052293
6 · The paper itself

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.

Indexed as

Escherichia coli ProteinsPeptidoglycanAnti-Bacterial AgentsATP-Binding Cassette, Sub-Family C ProteinsBacterial Outer Membrane ProteinsCarrier ProteinsCell WallCryoelectron MicroscopyEscherichia coliLipoproteinsMembrane Transport ProteinsAcrAB-TolC protein, E coliAcrA protein, E coliAnti-Bacterial AgentsATP-Binding Cassette, Sub-Family C ProteinsBacterial Outer Membrane ProteinsCarrier ProteinsEscherichia coli ProteinsLipoproteinsLpp protein, E coliMembrane Transport ProteinsPeptidoglycantraN protein, E coli

Identifiers

PMID34411576
PMCPMC8510974
OpenAlexW3193282310

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.