ArticlePLoS biology2012
Intracellular proton access in a Cl(-)/H(+) antiporter.
Article in PLoS biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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
29 citing papers in PubMed, 41 citations in OpenAlex.
- Structural basis of adenine nucleotides regulation and neurodegenerative pathology in ClC-3 exchanger.Nature communications · 2024Article
- Structural basis of pH-dependent activation in a CLC transporter.Nature structural & molecular biology · 2024Article
- The role of conformational change and key glutamic acid residues in the ClC-ec1 antiporter.Biophysical journal · 2023Article
- The Role of the Lysosomal ClCells · 2022Review
- 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
- Altering CLC stoichiometry by reducing non-polar side-chains at the dimerization interface.Journal of molecular biology · 2021Article
- Not so transport incompetent after all: Revisiting a CLC-7 mutant sheds new mechanistic light on lysosomal physiology.The Journal of general physiology · 2021Article
- Metabolic energy sensing by mammalian CLC anion/proton exchangers.EMBO reports · 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
- 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
- Structure of the CLC-1 chloride channel fromeLife · 2018Article
- Multiscale Kinetic Modeling Reveals an Ensemble of ClJournal of the American Chemical Society · 2018Article
- Chloride Ion Transport by theFrontiers in chemistry · 2018Article
- Molecular simulations and free-energy calculations suggest conformation-dependent anion binding to a cytoplasmic site as a mechanism for NaThe Journal of biological chemistry · 2017Article
- Helix O modulates voltage dependency of CLC-1.Pflugers Archiv : European journal of physiology · 2017Article
- The Origin of Coupled Chloride and Proton Transport in a ClJournal of the American Chemical Society · 2016Article
- Multiscale Simulations Reveal Key Aspects of the Proton Transport Mechanism in the ClC-ec1 Antiporter.Biophysical journal · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Chloride-transporting membrane proteins of the CLC family appear in two distinct mechanistic flavors: H(+)-gated Cl(-) channels and Cl(-)/H(+) antiporters. Transmembrane H(+) movement is an essential feature of both types of CLC. X-ray crystal structures of CLC antiporters show the Cl(-) ion pathway through these proteins, but the H(+) pathway is known only inferentially by two conserved glutamate residues that act as way-stations for H(+) in its path through the protein. The extracellular-facing H(+) transfer glutamate becomes directly exposed to aqueous solution during the transport cycle, but the intracellular glutamate E203, Glu(in), is buried within the protein. Two regions, denoted "polar" and "interfacial," at the intracellular surface of the bacterial antiporter CLC-ec1 are examined here as possible pathways by which intracellular aqueous protons gain access to Glu(in). Mutations at multiple residues of the polar region have little effect on antiport rates. In contrast, mutation of E202, a conserved glutamate at the protein-water boundary of the interfacial region, leads to severe slowing of the Cl(-)/H(+) antiport rate. An X-ray crystal structure of E202Y, the most strongly inhibited of these substitutions, shows an aqueous portal leading to Glu(in) physically blocked by cross-subunit interactions; moreover, this mutation has only minimal effect on a monomeric CLC variant, which necessarily lacks such interactions. The several lines of experiments presented argue that E202 acts as a water-organizer that creates a proton conduit connecting intracellular solvent with Glu(in).
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.