ArticleProceedings of the National Academy of Sciences of the United States of America2014
Structural basis for allosteric cross-talk between the asymmetric nucleotide binding sites of a heterodimeric ABC exporter.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 119 citations in OpenAlex.
- Capturing transient states of heterodimeric ABC transporter TM287/288 by time-resolved small-angle X-ray scattering.Biophysical journal · 2026Article
- Single-molecule dynamics reveal ATP binding alone powers substrate translocation by an ABC transporter.Nature communications · 2026Article
- Braess' Paradox in Enzyme Kinetics: Asymmetry from Population Balance without Direct Cooperativity.Journal of chemical theory and computation · 2026Article
- Structure and mechanism of a mycobacterial isoniazid efflux pump MsRv1273c/72c with a degenerate nucleotide-binding site.Nature communications · 2025Article
- Cryo-EM analyses unveil details of mechanism and targocil-II mediated inhibition of S. aureus WTA transporter TarGH.Nature communications · 2025Article
- Article
- The mycobacterial ABC transporter IrtAB employs a membrane-facing crevice for siderophore-mediated iron uptake.Nature communications · 2025Article
- Asymmetric conformations and lipid interactions shape the ATP-coupled cycle of a heterodimeric ABC transporter.Nature communications · 2023Article
- Estimating the true stability of the prehydrolytic outward-facing state in an ABC protein.eLife · 2023Article
- Deep mutational scan of a drug efflux pump reveals its structure-function landscape.Nature chemical biology · 2023Article
- The ABC transporter MsbA adopts the wide inward-open conformation inScience advances · 2022Article
- Drug-dependent inhibition of nucleotide hydrolysis in the heterodimeric ABC multidrug transporter PatAB from Streptococcus pneumoniae.The FEBS journal · 2022Article
- Structural identification of vasodilator binding sites on the SUR2 subunit.Nature communications · 2022Article
- Asymmetric drug binding in an ATP-loaded inward-facing state of an ABC transporter.Nature chemical biology · 2022Article
- The molecular evolution of function in the CFTR chloride channel.The Journal of general physiology · 2021Article
- Multidrug Resistance in Mammals and Fungi-From MDR to PDR: A Rocky Road from Atomic Structures to Transport Mechanisms.International journal of molecular sciences · 2021Review
- Structural and functional diversity calls for a new classification of ABC transporters.FEBS letters · 2020Review
- The first intracellular loop is essential for the catalytic cycle of the human ABCG2 multidrug resistance transporter.FEBS letters · 2020Article
- The role of the degenerate nucleotide binding site in type I ABC exporters.FEBS letters · 2020Review
- Structures of ABC transporters: handle with care.FEBS letters · 2020Review
2 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ATP binding cassette (ABC) transporters mediate vital transport processes in every living cell. ATP hydrolysis, which fuels transport, displays positive cooperativity in numerous ABC transporters. In particular, heterodimeric ABC exporters exhibit pronounced allosteric coupling between a catalytically impaired degenerate site, where nucleotides bind tightly, and a consensus site, at which ATP is hydrolyzed in every transport cycle. Whereas the functional phenomenon of cooperativity is well described, its structural basis remains poorly understood. Here, we present the apo structure of the heterodimeric ABC exporter TM287/288 and compare it to the previously solved structure with adenosine 5'-(β,γ-imido)triphosphate (AMP-PNP) bound at the degenerate site. In contrast to other ABC exporter structures, the nucleotide binding domains (NBDs) of TM287/288 remain in molecular contact even in the absence of nucleotides, and the arrangement of the transmembrane domains (TMDs) is not influenced by AMP-PNP binding, a notion confirmed by double electron-electron resonance (DEER) measurements. Nucleotide binding at the degenerate site results in structural rearrangements, which are transmitted to the consensus site via two D-loops located at the NBD interface. These loops owe their name from a highly conserved aspartate and are directly connected to the catalytically important Walker B motif. The D-loop at the degenerate site ties the NBDs together even in the absence of nucleotides and substitution of its aspartate by alanine is well-tolerated. By contrast, the D-loop of the consensus site is flexible and the aspartate to alanine mutation and conformational restriction by cross-linking strongly reduces ATP hydrolysis and substrate transport.
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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.