ArticleProceedings of the National Academy of Sciences of the United States of America2009
The assembled structure of a complete tripartite bacterial multidrug efflux pump.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 papers.
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Who cites it
147 citing papers in PubMed, 285 citations in OpenAlex.
- A review of research progress on periplasmic adaptor proteins in bacterial tripartite pumps.Frontiers in microbiology · 2026Review
- The Resistance-Nodulation-Division efflux pump EefABC is highly conserved within lineages ofMicrobial genomics · 2026Article
- Computer Simulations of Multidrug Efflux Pumps of the Resistance-Nodulation-Cell Division Superfamily.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Bacterial Proteomics and Antibiotic Resistance Identification: Is Single-Cell Analysis a Worthwhile Pursuit?Pathogens (Basel, Switzerland) · 2025Review
- Beyond antibiotics: exploring multifaceted approaches to combat bacterial resistance in the modern era: a comprehensive review.Frontiers in cellular and infection microbiology · 2025Review
- Comparative Genome Analysis of PiscineMicroorganisms · 2024Article
- Quantifying bacterial efflux within subcellular domains ofApplied and environmental microbiology · 2024Article
- Mechanisms of Copper Selectivity and Release by the Metallochaperone CusF: Insights from CO-Binding, Rapid-Freeze-Quench EXAFS, and Unnatural Amino Acid Substitution.Inorganic chemistry · 2024Article
- Kinetic study of membrane protein interactions: from three to two dimensions.Scientific reports · 2024Article
- The Combination of Antibiotic and Non-Antibiotic Compounds Improves Antibiotic Efficacy against Multidrug-Resistant Bacteria.International journal of molecular sciences · 2023Review
- Conformational restriction shapes the inhibition of a multidrug efflux adaptor protein.Nature communications · 2023Article
- The Alternating Access Mechanism in Mammalian Multidrug Resistance Transporters and Their Bacterial Homologs.Membranes · 2023Article
- Analysis of Cellular Damage Resulting from Exposure of Bacteria to Graphene Oxide and Hybrids Using Fourier Transform Infrared Spectroscopy.Antibiotics (Basel, Switzerland) · 2023Article
- Review
- Global genomic epidemiology of chromosomally mediated non-enzymatic carbapenem resistance inFrontiers in microbiology · 2023Article
- The role of bacterial transport systems in the removal of host antimicrobial peptides in Gram-negative bacteria.FEMS microbiology reviews · 2022Review
- Review
- Importance of RpoD- and Non-RpoD-Dependent Expression of Horizontally Acquired Genes in Cupriavidus metallidurans.Microbiology spectrum · 2022Article
- Molecular Determinants for OMF Selectivity in Tripartite RND Multidrug Efflux Systems.Antibiotics (Basel, Switzerland) · 2022Article
- Multidrug Resistance (MDR): A Widespread Phenomenon in Pharmacological Therapies.Molecules (Basel, Switzerland) · 2022Review
87 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Bacteria like Escherichia coli and Pseudomonas aeruginosa expel drugs via tripartite multidrug efflux pumps spanning both inner and outer membranes and the intervening periplasm. In these pumps a periplasmic adaptor protein connects a substrate-binding inner membrane transporter to an outer membrane-anchored TolC-type exit duct. High-resolution structures of all 3 components are available, but a pump model has been precluded by the incomplete adaptor structure, because of the apparent disorder of its N and C termini. We reveal that the adaptor termini assemble a beta-roll structure forming the final domain adjacent to the inner membrane. The completed structure enabled in vivo cross-linking to map intermolecular contacts between the adaptor AcrA and the transporter AcrB, defining a periplasmic interface between several transporter subdomains and the contiguous beta-roll, beta-barrel, and lipoyl domains of the adaptor. With short and long cross-links expressed as distance restraints, the flexible linear topology of the adaptor allowed a multidomain docking approach to model the transporter-adaptor complex, revealing that the adaptor docks to a transporter region of comparative stability distinct from those key to the proposed rotatory pump mechanism, putative drug-binding pockets, and the binding site of inhibitory DARPins. Finally, we combined this docking with our previous resolution of the AcrA hairpin-TolC interaction to develop a model of the assembled tripartite complex, satisfying all of the experimentally-derived distance constraints. This AcrA(3)-AcrB(3)-TolC(3) model presents a 610,000-Da, 270-A-long efflux pump crossing the entire bacterial cell envelope.
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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.