ArticleProceedings of the National Academy of Sciences of the United States of America2018
Guanidinium export is the primal function of SMR family transporters.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 89 citations in OpenAlex.
- Gdx mediates low-affinity Cs⁺/H⁺ antiport and confers cesium resistance inEngineering microbiology · 2026Article
- Cyanobacterial Biofertilizer Production by Guanidine-Producing Enzymes.ACS synthetic biology · 2026Review
- Deciphering guanidine assimilation and riboswitch-based gene regulation in cyanobacteria for synthetic biology applications.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Metabolic Origin, Role and Fate of the Denaturant Guanidine.Microbial biotechnology · 2025Article
- Demethylation of methylguanidine by a stepwise dioxygenase and lyase reaction.Nature communications · 2025Article
- Quantification of Membrane Protein Conformational Free Energy from Mutations and a Single Atom.Journal of the American Chemical Society · 2025Article
- Guanidine aptamers are present in vertebrate RNAs associated with calcium signaling and neuromuscular function.Nature communications · 2025Article
- From lab reagent to metabolite: the riboswitch ligand guanidine as a relevant compound in bacterial physiology.Journal of bacteriology · 2025Review
- Protocol for purifying and reconstituting a vacuole membrane transporter Ypq1 into proteoliposomes.STAR protocols · 2024Article
- Article
- The current riboswitch landscape inMicrobiology (Reading, England) · 2024Review
- Cooperative binding of bivalent ligands yields new insights into the guanidine-II riboswitch.NAR genomics and bioinformatics · 2024Article
- 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
- 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
- Lysosomal membrane transporter purification and reconstitution for functional studies.Molecular biology of the cell · 2024Article
- Infrared Photoactivation Enables Improved Native Top-Down Mass Spectrometry of Transmembrane Proteins.Analytical chemistry · 2023Article
- Identification and expression of small multidrug resistance transporters in early-branching anaerobic fungi.Protein science : a publication of the Protein Society · 2023Article
- Antibacterial Effect of 16 Essential Oils and Modulation ofAntibiotics (Basel, Switzerland) · 2023Article
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4 authors at 1 institution in 1 country.
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Abstract
The small multidrug resistance (SMR) family of membrane proteins is prominent because of its rare dual topology architecture, simplicity, and small size. Its best studied member, EmrE, is an important model system in several fields related to membrane protein biology, from evolution to mechanism. But despite decades of work on these multidrug transporters, the native function of the SMR family has remained a mystery, and many highly similar SMR homologs do not transport drugs at all. Here we establish that representative SMR proteins, selected from each of the major clades in the phylogeny, function as guanidinium ion exporters. Drug-exporting SMRs are all clustered in a single minority clade. Using membrane transport experiments, we show that these guanidinium exporters, which we term Gdx, are very selective for guanidinium and strictly and stoichiometrically couple its export with the import of two protons. These findings draw important mechanistic distinctions with the notably promiscuous and weakly coupled drug exporters like EmrE.
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