ArticleThe Journal of general physiology2015
Asymmetric protonation of EmrE.
Article in The Journal of general physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 65 citations in OpenAlex.
- Proton hopping and secondary gating reveal a universal transport mechanism in a minimal bacterial transporter EmrE.Biophysical journal · 2026Article
- Protonated Structure of EmrE Reveals C-terminal Tail Gating Mechanism.bioRxiv : the preprint server for biology · 2026Article
- Multidrug resistance transporter EmrE is only moderately sensitive to lipid composition.Biophysical journal · 2026Article
- Conduction pathway for potassium through theeLife · 2025Article
- Conduction pathway for potassium through the E. coli pump KdpFABC.bioRxiv : the preprint server for biology · 2025Article
- 18-Crown-6-ether Utilizes Distinct Allosteric Interactions to Uncouple Transport by the Multidrug Efflux Pump EmrE.Biochemistry · 2025Article
- The C-terminus of the multi-drug efflux pump EmrE prevents proton leak by gating transport.eLife · 2025Article
- Polar Networks Mediate Ion Conduction of the SARS-CoV-2 Envelope Protein.Journal of the American Chemical Society · 2025Article
- Kinetic Diagram Analysis: A Python Library for Calculating Steady-State Observables of Biochemical Systems Analytically.Journal of chemical theory and computation · 2024Article
- Kinetic Diagram Analysis: A Python Library for Calculating Steady-State Observables of Biochemical Systems Analytically.bioRxiv : the preprint server for biology · 2024Article
- Functional promiscuity of small multidrug resistance transporters from Staphylococcus aureus, Pseudomonas aeruginosa, and Francisella tularensis.Molecular microbiology · 2024Article
- Transport of metformin metabolites by guanidinium exporters of the small multidrug resistance family.The Journal of general physiology · 2024Article
- Review
- Energy coupling and stoichiometry of ZneLife · 2023Article
- Atomic structure of the open SARS-CoV-2 E viroporin.Science advances · 2023Article
- Microsecond Motion of the Bacterial Transporter EmrE in Lipid Bilayers.Journal of the American Chemical Society · 2023Article
- Activating alternative transport modes in a multidrug resistance efflux pump to confer chemical susceptibility.Nature communications · 2022Article
- Still rocking in the structural era: A molecular overview of the small multidrug resistance (SMR) transporter family.The Journal of biological chemistry · 2022Review
- Detergent-Free Isolation of Membrane Proteins and Strategies to Study Them in a Near-Native Membrane Environment.Biomolecules · 2022Review
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4 authors at 1 institution in 1 country.
Funding
Abstract
The small multidrug resistance transporter EmrE is a homodimer that uses energy provided by the proton motive force to drive the efflux of drug substrates. The pKa values of its "active-site" residues--glutamate 14 (Glu14) from each subunit--must be poised around physiological pH values to efficiently couple proton import to drug export in vivo. To assess the protonation of EmrE, pH titrations were conducted with (1)H-(15)N TROSY-HSQC nuclear magnetic resonance (NMR) spectra. Analysis of these spectra indicates that the Glu14 residues have asymmetric pKa values of 7.0 ± 0.1 and 8.2 ± 0.3 at 45°C and 6.8 ± 0.1 and 8.5 ± 0.2 at 25°C. These pKa values are substantially increased compared with typical pKa values for solvent-exposed glutamates but are within the range of published Glu14 pKa values inferred from the pH dependence of substrate binding and transport assays. The active-site mutant, E14D-EmrE, has pKa values below the physiological pH range, consistent with its impaired transport activity. The NMR spectra demonstrate that the protonation states of the active-site Glu14 residues determine both the global structure and the rate of conformational exchange between inward- and outward-facing EmrE. Thus, the pKa values of the asymmetric active-site Glu14 residues are key for proper coupling of proton import to multidrug efflux. However, the results raise new questions regarding the coupling mechanism because they show that EmrE exists in a mixture of protonation states near neutral pH and can interconvert between inward- and outward-facing forms in multiple different protonation states.
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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.