ArticleJournal of the American Chemical Society2014
Intrinsic conformational plasticity of native EmrE provides a pathway for multidrug resistance.
Article in Journal of the American Chemical Society, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed.
- Multidrug resistance transporter EmrE is only moderately sensitive to lipid composition.Biophysical journal · 2026Article
- Quantification of Membrane Protein Conformational Free Energy from Mutations and a Single Atom.Journal of the American Chemical Society · 2025Article
- Dipolar Recoupling in Rotating Solids.Chemical reviews · 2024Review
- Peripheral positions encode transport specificity in the small multidrug resistance exporters.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Dynamics underlie the drug recognition mechanism by the efflux transporter EmrE.Nature communications · 2024Article
- Characterization of nanodisc-forming peptides for membrane protein studies.Journal of colloid and interface science · 2024Article
- Microsecond Motion of the Bacterial Transporter EmrE in Lipid Bilayers.Journal of the American Chemical Society · 2023Article
- Enhancing the stability and homogeneity of non-ionic polymer nanodiscs by tuning electrostatic interactions.Journal of colloid and interface science · 2023Article
- Still rocking in the structural era: A molecular overview of the small multidrug resistance (SMR) transporter family.The Journal of biological chemistry · 2022Review
- High-pH structure of EmrE reveals the mechanism of proton-coupled substrate transport.Nature communications · 2022Article
- 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
- Structural Insights into Transporter-Mediated Drug Resistance in Infectious Diseases.Journal of molecular biology · 2021Review
- Assessing the Role of Lipids in the Molecular Mechanism of Membrane Proteins.International journal of molecular sciences · 2021Review
- Structure and dynamics of the drug-bound bacterial transporter EmrE in lipid bilayers.Nature communications · 2021Article
- Site-specific resolution of anionic residues in proteins using solid-state NMR spectroscopy.Journal of biomolecular NMR · 2020Article
- Simultaneous recording of intra- and inter-residue linking experiments for backbone assignments in proteins at MAS frequencies higher than 60 kHz.Journal of biomolecular NMR · 2020Article
- Inducing conformational preference of the membrane protein transporter EmrE through conservative mutations.eLife · 2019Article
- Identification of an Alternating-Access Dynamics Mutant of EmrE with Impaired Transport.Journal of molecular biology · 2019Article
- Opportunities and Challenges of Backbone, Sidechain, and RDC Experiments to Study Membrane Protein Dynamics in a Detergent-Free Lipid Environment Using Solution State NMR.Frontiers in molecular biosciences · 2019Review
- The C terminus of the bacterial multidrug transporter EmrE couples drug binding to proton release.The Journal of biological chemistry · 2018Article
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Authors and funding
5 authors.
Funding
Abstract
EmrE is a multidrug resistance efflux pump with specificity to a wide range of antibiotics and antiseptics. To obtain atomic-scale insight into the attributes of the native state that encodes the broad specificity, we used a hybrid of solution and solid-state NMR methods in lipid bilayers and bicelles. Our results indicate that the native EmrE dimer oscillates between inward and outward facing structural conformations at an exchange rate (k(ex)) of ~300 s(-1) at 37 °C (millisecond motions), which is ~50-fold faster relative to the tetraphenylphosphonium (TPP(+)) substrate-bound form of the protein. These observables provide quantitative evidence that the rate-limiting step in the TPP(+) transport cycle is not the outward-inward conformational change in the absence of drug. In addition, using differential scanning calorimetry, we found that the width of the gel-to-liquid crystalline phase transition was 2 °C broader in the absence of the TPP(+) substrate versus its presence, which suggested that changes in transporter dynamics can impact the phase properties of the membrane. Interestingly, experiments with cross-linked EmrE showed that the millisecond inward-open to outward-open dynamics was not the culprit of the broadening. Instead, the calorimetry and NMR data supported the conclusion that faster time scale structural dynamics (nanosecond-microsecond) were the source and therefore impart the conformationally plastic character of native EmrE capable of binding structurally diverse substrates. These findings provide a clear example how differences in membrane protein transporter structural dynamics between drug-free and bound states can have a direct impact on the physical properties of the lipid bilayer in an allosteric fashion.
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