ArticleNature structural & molecular biology2020
An embedded lipid in the multidrug transporter LmrP suggests a mechanism for polyspecificity.
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.
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Who cites it
48 citing papers in PubMed, 77 citations in OpenAlex.
- Miniprotein inhibitors of thebioRxiv : the preprint server for biology · 2026Article
- Diverse regulation of functional dimerization of a sugar transporter by different interfacial lipids.Nature communications · 2026Article
- Drug-bound outward-facing conformation of a heterodimeric ABC exporter suggests a putative mechanism of drug translocation.Nature communications · 2025Article
- Modeling protein conformational ensembles by guiding AlphaFold2 with Double Electron Electron Resonance (DEER) distance distributions.Nature communications · 2025Article
- Understanding, inhibiting, and engineering membrane transporters with high-throughput mutational screens.Cell chemical biology · 2025Review
- Fluctuating hydrogen-bond network of the Hv1 ion channel.Computational and structural biotechnology journal · 2025Article
- The conserved lysine residue in transmembrane helix 5 is pivotal for the cytoplasmic gating of the L-amino acid transporters.PNAS nexus · 2025Article
- Structures of the Mycobacterium tuberculosis efflux pump EfpA reveal the mechanisms of transport and inhibition.Nature communications · 2024Article
- Coupling the role of lipids to the conformational dynamics of the ABC transporter P-glycoprotein.Biophysical journal · 2024Article
- Review
- Structures of the essential efflux pump EfpA fromResearch square · 2024Article
- Major facilitator superfamily efflux pumps in human pathogens: Role in multidrug resistance and beyond.Current research in microbial sciences · 2024Article
- Role of environmental specificity in CASP results.BMC bioinformatics · 2023Article
- Structural Insights into the Binding and Degradation Mechanisms of Protoporphyrin IX by the Translocator Protein TSPO.JACS Au · 2023Article
- Article
- Darobactin B Stabilises a Lateral-Closed Conformation of the BAM Complex in E. coli Cells.Angewandte Chemie (International ed. in English) · 2023Article
- Darobactin B Stabilises a Lateral-Closed Conformation of the BAM Complex inAngewandte Chemie (Weinheim an der Bergstrasse, Germany) · 2023Article
- Cryo-EM structure of antibacterial efflux transporter QacA from Staphylococcus aureus reveals a novel extracellular loop with allosteric role.The EMBO journal · 2023Article
- Interaction of Hoechst 33342 with POPC Membranes at Different pH Values.Molecules (Basel, Switzerland) · 2023Article
- Inhibition of Multidrug Efflux Pumps Belonging to the Major Facilitator Superfamily in Bacterial Pathogens.Biomedicines · 2023Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
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.
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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.