ArticleThe Journal of biological chemistry2015
A structured loop modulates coupling between the substrate-binding and dimerization domains in the multidrug resistance transporter EmrE.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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.
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.
Who cites it
14 citing papers in PubMed, 26 citations in OpenAlex.
- Functional promiscuity of small multidrug resistance transporters from Staphylococcus aureus, Pseudomonas aeruginosa, and Francisella tularensis.Molecular microbiology · 2024Article
- The culmination of multidrug-resistant efflux pumps vs. meager antibiotic arsenal era: Urgent need for an improved new generation of EPIs.Frontiers in microbiology · 2023Review
- Activating alternative transport modes in a multidrug resistance efflux pump to confer chemical susceptibility.Nature communications · 2022Article
- Bacterial Multidrug Efflux Pumps at the Frontline of Antimicrobial Resistance: An Overview.Antibiotics (Basel, Switzerland) · 2022Review
- Article
- Asymmetric protonation of glutamate residues drives a preferred transport pathway in EmrE.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Plant-derived secondary metabolites as the main source of efflux pump inhibitors and methods for identification.Journal of pharmaceutical analysis · 2020Review
- Effect of Site-Specific Intermolecular Lysine-Tryptophan Interactions on the Aggregation of Gramicidin-Based Peptides Leading to Pore Formation in Lipid Membranes.The Journal of membrane biology · 2018Article
- Structure of theProceedings of the National Academy of Sciences of the United States of America · 2018Article
- Assessing Interactions Between a Polytopic Membrane Protein and Lipid Bilayers Using Differential Scanning Calorimetry and Solid-State NMR.The journal of physical chemistry. B · 2018Article
- Influence of quaternary cation compound on the size of theBiochemistry and biophysics reports · 2018Article
- Afterglow Solid-State NMR Spectroscopy.Methods in molecular biology (Clifton, N.J.) · 2018Article
- Protonation of a glutamate residue modulates the dynamics of the drug transporter EmrE.Nature chemical biology · 2016Article
- Protonation-dependent conformational dynamics of the multidrug transporter EmrE.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Secondary active transporters undergo large conformational changes to facilitate the efflux of substrates across the lipid bilayer. Among the smallest known transport proteins are members of the small multidrug resistance (SMR) family that are composed of four transmembrane (TM) domains and assemble into dimers. An unanswered question in the SMR field is how the dimerization domain (TM4) is coupled with the substrate-binding chamber (TM1-3). To provide insight for this essential aspect of ion-coupled transport, we carried out a structure-function study on the SMR protein EmrE using solid-state NMR spectroscopy in lipid bilayers and resistance assays in Escherichia coli. The chemical shifts for EmrE were consistent with β-strand secondary structure for the loop connecting TM3 and TM4. Based on these structural results, EmrE mutants were created to ascertain whether a specific loop length and composition were necessary for function. A linker encompassing six extra Gly residues relative to wild-type EmrE failed to give resistance; however, the number of residues in the loop was not the only criterion for a functional efflux pump. Replacement of the central hydrophobic residue with Gly (L83G) also conferred no ethidium resistance phenotype, which supported the conclusion that the structure and length of the loop were both essential for ion-coupled transport. Taken together with a bioinformatics analysis, a structured linker is likely conserved across the SMR family to play an active role in mediating the conformational switch between inward-open and outward-open states necessary for drug efflux. These findings underscore the important role loops can play in mediating efflux.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.