Evidence map›Paper›PMID 32719456›Full record

ArticleNature structural & molecular biology2020

An embedded lipid in the multidrug transporter LmrP suggests a mechanism for polyspecificity.

Vincent Debruycker, Andrew Hutchin, Matthieu Masureel, Emel Ficici, Chloé Martens, Pierre Legrand, Richard A Stein, Hassane S Mchaourab, José D Faraldo-Gómez, Han Remaut and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Nature structural & molecular biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
4.5field-weighted citation impact, top 3% 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

48 citing papers in PubMed, 77 citations in OpenAlex.

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  15. Antibiotics (Basel, Switzerland) · 2023
    Article
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  17. Darobactin B Stabilises a Lateral-Closed Conformation of the BAM Complex inAngewandte Chemie (Weinheim an der Bergstrasse, Germany) · 2023
    Article
  18. Article
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  20. Review
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

11 authors at 5 institutions in 3 countries.

Vincent Debruycker *Laboratory for the Structure and Function of Biological Membranes, Center for Structural Biology and Bioinformatics, Université Libre de Bruxelles, Brussels, Belgium.
Andrew Hutchin *Laboratory for the Structure and Function of Biological Membranes, Center for Structural Biology and Bioinformatics, Université Libre de Bruxelles, Brussels, Belgium.ORCID http://orcid.org/0000-0002-4961-6995
Matthieu MasureelLaboratory for the Structure and Function of Biological Membranes, Center for Structural Biology and Bioinformatics, Université Libre de Bruxelles, Brussels, Belgium.
Emel FiciciTheoretical Molecular Biophysics Laboratory, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Chloé MartensLaboratory for the Structure and Function of Biological Membranes, Center for Structural Biology and Bioinformatics, Université Libre de Bruxelles, Brussels, Belgium.
Pierre LegrandSynchrotron SOLEIL, L'Orme des Merisiers, Saint-Aubin 91192, Gif sur Yvette, France.ORCID http://orcid.org/0000-0003-2431-2255
Richard A SteinDepartment of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN, USA.
Hassane S MchaourabDepartment of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN, USA.
José D Faraldo-GómezTheoretical Molecular Biophysics Laboratory, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Han RemautStructural Biology Brussels, Vrije Universiteit Brussel, Brussels, Belgium.ORCID http://orcid.org/0000-0002-9775-4102
Cédric GovaertsLaboratory for the Structure and Function of Biological Membranes, Center for Structural Biology and Bioinformatics, Université Libre de Bruxelles, Brussels, Belgium. cgovaert@ulb.ac.be.ORCID http://orcid.org/0000-0003-3218-3262
Université Libre de Bruxelles · BENational Institutes of Health · USVanderbilt University Medical Center · USSynchrotron soleil · FRVrije Universiteit Brussel · BE

Funding

Molecular Mechanisms in Membrane Bioenergetics, Transport and SignalingZIAHL006203 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI FARALDO-GÓMEZ, JOSE · 2015 to 2023
$15.4M
Structural Dynamics of Multi-drug TransportersR01GM077659 · NIGMS · VANDERBILT UNIVERSITY · PI MCHAOURAB, HASSANE S · 2006 to 2023
$5.0M
Biotechnology and Biological Sciences Research Council BB/M012573/1NIGMS NIH HHS R01 GM077659
6 · The paper itself

Abstract

Multidrug efflux pumps present a challenge to the treatment of bacterial infections, making it vitally important to understand their mechanism of action. Here, we investigate the nature of substrate binding within Lactococcus lactis LmrP, a prototypical multidrug transporter of the major facilitator superfamily. We determined the crystal structure of LmrP in a ligand-bound outward-open state and observed an embedded lipid in the binding cavity of LmrP, an observation supported by native mass spectrometry analyses. Molecular dynamics simulations suggest that the anionic lipid stabilizes the observed ligand-bound structure. Mutants engineered to disrupt binding of the embedded lipid display reduced transport of some, but not all, antibiotic substrates. Our results suggest that a lipid within the binding cavity could provide a malleable hydrophobic component that allows adaptation to the presence of different substrates, helping to explain the broad specificity of this protein and possibly other multidrug transporters.

Indexed as

Anti-Bacterial AgentsBacterial ProteinsBinding SitesBiological TransportCrystallography, X-RayLactococcus lactisLigandsMembrane Transport ProteinsMolecular Dynamics SimulationPhosphatidylglycerolsProtein ConformationSubstrate SpecificityAnti-Bacterial AgentsBacterial ProteinsLigandsMembrane Transport ProteinsPhosphatidylglycerols

Identifiers

PMID32719456
PMCPMC7951658
OpenAlexW3044291258

What OpenQuestion holds

Textmetadata
LicenceTDM
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.