ArticleNature structural & molecular biology2012
Synergistic substrate binding determines the stoichiometry of transport of a prokaryotic H(+)/Cl(-) exchanger.
Article in Nature structural & molecular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
44 citing papers in PubMed, 72 citations in OpenAlex.
- Molecular mechanism of exchange coupling in CLC chloride/proton antiporters.Nature communications · 2026Article
- Site-directed mutagenesis at the Glu78 in Ec-NhaA transporter impacting ion exchange: a biophysical study.European biophysics journal : EBJ · 2024Article
- Review
- Fluoride Transport and Inhibition Across CLC Transporters.Handbook of experimental pharmacology · 2024Article
- The role of conformational change and key glutamic acid residues in the ClC-ec1 antiporter.Biophysical journal · 2023Article
- Multiscale kinetic analysis of proteins.Current opinion in structural biology · 2022Review
- An endoplasmic reticulum-localized cytochromeProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Simulation of pH-Dependent Conformational Transitions in Membrane Proteins: The CLC-ec1 ClMolecules (Basel, Switzerland) · 2021Article
- Toward a Multipathway Perspective: pH-Dependent Kinetic Selection of Competing Pathways and the Role of the Internal Glutamate in ClThe journal of physical chemistry. B · 2021Article
- Q-cubed mutant cues clues to CLC antiport mechanism.The Journal of general physiology · 2021Article
- FFrontiers in microbiology · 2021Article
- Cryo-EM structure of the lysosomal chloride-proton exchanger CLC-7 in complex with OSTM1.eLife · 2020Article
- Divergent CleLife · 2020Article
- A CLC-ec1 mutant reveals global conformational change and suggests a unifying mechanism for the CLC CleLife · 2020Article
- Local conformational dynamics regulating transport properties of a ClJournal of computational chemistry · 2020Article
- Dynamical model of the CLC-2 ion channel reveals conformational changes associated with selectivity-filter gating.PLoS computational biology · 2020Article
- Mutation of external glutamate residue reveals a new intermediate transport state and anion binding site in a CLC ClProceedings of the National Academy of Sciences of the United States of America · 2019Article
- Modulating the Chemical Transport Properties of a Transmembrane Antiporter via Alternative Anion Flux.Journal of the American Chemical Society · 2018Article
- Modulation of ClC-3 gating and proton/anion exchange by internal and external protons and the anion selectivity filter.The Journal of physiology · 2018Article
- A CLC-type FNature structural & molecular biology · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Active exchangers dissipate the gradient of one substrate to accumulate nutrients, export xenobiotics and maintain cellular homeostasis. Mechanistic studies have suggested that two fundamental properties are shared by all exchangers: substrate binding is antagonistic, and coupling is maintained by preventing shuttling of the empty transporter. The CLC H(+)/Cl(-) exchangers control the homeostasis of cellular compartments in most living organisms, but their transport mechanism remains unclear. We show that substrate binding to CLC-ec1 is synergistic rather than antagonistic: chloride binding induces protonation of a crucial glutamate. The simultaneous binding of H(+) and Cl(-) gives rise to a fully loaded state that is incompatible with conventional transport mechanisms. Mutations in the Cl(-) transport pathway identically alter the stoichiometries of H(+)/Cl(-) exchange and binding. We propose that the thermodynamics of synergistic substrate binding, rather than the kinetics of conformational changes and ion binding, determine the stoichiometry of transport.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.