ArticleNature chemical biology2022
Asymmetric drug binding in an ATP-loaded inward-facing state of an ABC transporter.
Article in Nature chemical biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 30 citations in OpenAlex.
- Drug-bound outward-facing conformation of a heterodimeric ABC exporter suggests a putative mechanism of drug translocation.Nature communications · 2025Article
- Conformational dynamics and asymmetry in multimodal inhibition of membrane-bound pyrophosphatases.eLife · 2025Article
- Structure and mechanism of a mycobacterial isoniazid efflux pump MsRv1273c/72c with a degenerate nucleotide-binding site.Nature communications · 2025Article
- Structural basis for autoinhibition by the dephosphorylated regulatory domain of Ycf1.Nature communications · 2024Article
- Disruption of the bacterial OLE RNP complex impairs growth on alternative carbon sources.PNAS nexus · 2024Article
- Genome wide structural prediction of ABC transporter systems inFrontiers in microbiology · 2024Article
- Spectroscopically Orthogonal Labelling to Disentangle Site-Specific Nitroxide Label Distributions.Applied magnetic resonance · 2024Article
- Asymmetric conformations and lipid interactions shape the ATP-coupled cycle of a heterodimeric ABC transporter.Nature communications · 2023Article
- Interaction of Hoechst 33342 with POPC Membranes at Different pH Values.Molecules (Basel, Switzerland) · 2023Article
- Structures of the CcmABCD heme release complex at multiple states.Nature communications · 2022Article
- EPR Spectroscopy Provides New Insights into Complex Biological Reaction Mechanisms.The journal of physical chemistry. B · 2022Review
- Expression of Bacillus subtilis ABCF antibiotic resistance factor VmlR is regulated by RNA polymerase pausing, transcription attenuation, translation attenuation and (p)ppGpp.Nucleic acids research · 2022Article
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Substrate efflux by ATP-binding cassette (ABC) transporters, which play a major role in multidrug resistance, entails the ATP-powered interconversion between transporter intermediates. Despite recent progress in structure elucidation, a number of intermediates have yet to be visualized and mechanistically interpreted. Here, we combine cryogenic-electron microscopy (cryo-EM), double electron-electron resonance spectroscopy and molecular dynamics simulations to profile a previously unobserved intermediate of BmrCD, a heterodimeric multidrug ABC exporter from Bacillus subtilis. In our cryo-EM structure, ATP-bound BmrCD adopts an inward-facing architecture featuring two molecules of the substrate Hoechst-33342 in a striking asymmetric head-to-tail arrangement. Deletion of the extracellular domain capping the substrate-binding chamber or mutation of Hoechst-coordinating residues abrogates cooperative stimulation of ATP hydrolysis. Together, our findings support a mechanistic role for symmetry mismatch between the nucleotide binding and the transmembrane domains in the conformational cycle of ABC transporters and is of notable importance for rational design of molecules for targeted ABC transporter inhibition.
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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.