The DOI matches its Crossref record.
F−/Cl− selectivity in CLCF-type F−/H+ antiporters
Abstract
Many bacterial species protect themselves against environmental F− toxicity by exporting this anion from the cytoplasm via CLCF F−/H+ antiporters, a subclass of CLC superfamily anion transporters. Strong F− over Cl− selectivity is biologically essential for these membrane proteins because Cl− is orders of magnitude more abundant in the biosphere than F−. Sequence comparisons reveal differences between CLCFs and canonical Cl−-transporting CLCs within regions that, in the canonical CLCs, coordinate Cl− ion and govern anion transport. A phylogenetic split within the CLCF clade, manifested in sequence divergence in the vicinity of this ion-binding center, raises the possibility that these two CLCF subclades might exhibit differences in anion selectivity. Several CLCF homologues from each subclade were examined for F−/Cl− selectivity of anion transport and equilibrium binding. Differences in both of these anion-selectivity metrics correlate with sequence divergence among CLCFs. Chimeric constructs identify two residues in this region that largely account for the subclade differences in selectivity. In addition, these experiments serendipitously uncovered an unusually steep, Cl−-specific voltage dependence of transport that greatly enhances F− selectivity at low voltage.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
ClCF transporters can transport both chloride and fluoride ions or only fluoride.
“While ClCF transporters can transport both chloride and fluoride ions or only fluoride, CrcB channels are highly selective for fluoride (6, 12).”
From Adaptive evolution of Pseudomonas putida in the presence of fluoride exposes novel functions of a benzoate transporter (2026) · cites this paper as [12]
CrcB channels are highly selective for fluoride.
“While ClCF transporters can transport both chloride and fluoride ions or only fluoride, CrcB channels are highly selective for fluoride (6, 12).”
From Adaptive evolution of Pseudomonas putida in the presence of fluoride exposes novel functions of a benzoate transporter (2026) · cites this paper as [12]
1289 catalyzed robust fluoride efflux from liposomes, with a unitary transport rate of 830 ± 20 ions/second.
“1289 catalyzed robust fluoride efflux from liposomes, with a unitary transport rate of 830 ± 20 ions/second, in line with rates measured for other CLCF transporters (43).”
From Fluoride export is required for the competitive fitness of pathogenic microorganisms in dental biofilm models (2024) · cites this paper as [43]
The fluoride-binding motifs in 1289 and 1290 are distinct from the selectivity filter sequences of CLC chloride transporters.
“which are quite distinct from the selectivity filter sequences of CLC chloride transporters (22, 43).”
From Fluoride export is required for the competitive fitness of pathogenic microorganisms in dental biofilm models (2024) · cites this paper as [43]
Mutating each of three conserved Bpe residues coordinating the F- densities (F82, F85, N43) did not produce single-channel activity in electrical recordings, but anion-dump experiments reveal dramatic changes in F- permeation.
“We next examined the functional consequences of mutating each of three conserved Bpe residues coordinating the F- densities: F82, F85, and N43. We did not observe single-channel activity in electrical recordings, but more sensitive “anion-dump” experiments22,23 reveal dramatic changes in F- permeation”
From Crystal structures of a double-barrelled fluoride ion channel (2015) · cites this paper as [23]
Fluoride-specific CLCFs can be identified by three signature sequences: GNNLI/GMGLI in the N-terminal domain, GREGT/V at the transport machinery, and GEVTP in the C-terminal domain.
“Fluoride-specific CLCFs can be identified based on three signature sequences: the GNNLI/GMGLI in the N-terminal domain that defines ion selectivity, GREGT/V at the heart of the transport machinery, and the GEVTP sequence in the C-terminal domain that contributes fluoride-binding residues77–79.”
From The link between ancient microbial fluoride resistance mechanisms and bioengineering organofluorine degradation or synthesis (2024) · cites this paper as [78]
CLCFs are >80-fold selective for fluoride over chloride.
“Biochemical experiments have demonstrated that CLCFs are >80-fold selective for fluoride over chloride, the halide that is closest in size and the main biological anion77,78.”
From The link between ancient microbial fluoride resistance mechanisms and bioengineering organofluorine degradation or synthesis (2024) · cites this paper as [78]
CLCF proteins have been demonstrated to be F−/H+ antiporters with high specificity for F− compared with other anions, unlike chloride-specific CLCs.
“These CLCF proteins have been demonstrated to be F−/H+ antiporters with high specificity for F− compared with other anions (174), unlike chloride-specific CLCs that tend to have more promiscuous activities.”
From Toward the development of a molecular toolkit for the microbial remediation of per-and polyfluoroalkyl substances (2024) · cites this paper as [174]
The transporters harness the transmembrane proton gradient to export one F− in exchange for one H+, and the unitary transport rates of different characterized homologues range from ~400-1000 ions per second.
“The transporters harness the transmembrane proton gradient to export one F− in exchange for one H+, and the unitary transport rates of different characterized homologues ranges from ~400–1000 ions per second (1, 50).”
From Membrane exporters of fluoride ion (2021) · cites this paper as [50]
Mutagenesis experiments showed that M79 contributes to F−/Cl− selectivity in CLCF proteins, and conversion to asparagine reduces selectivity in a close homologue of the E. casseliflavus protein.
“Mutagenesis experiments showed that this methionine contributes to F−/Cl− selectivity in the CLCF proteins, and conversion to the straightforwardly polar asparagine reduces selectivity in a close homologue of the E. casseliflavus protein(50).”
From Membrane exporters of fluoride ion (2021) · cites this paper as [50]
F− transport is abolished in neutral mutants E118Q and E118A.
“In accord with the proposal that electrostatic repulsion by the E118 carboxylate hastens F− along the permeation pathway, F− transport is abolished in neutral mutants E118Q and E118A – because the F− binding affinity is over an order of magnitude higher in these mutants compared with wildtype(50, 52).”
From Membrane exporters of fluoride ion (2021) · cites this paper as [50]
F− binding affinity is over an order of magnitude higher in E118Q and E118A mutants compared with wildtype.
“In accord with the proposal that electrostatic repulsion by the E118 carboxylate hastens F− along the permeation pathway, F− transport is abolished in neutral mutants E118Q and E118A – because the F− binding affinity is over an order of magnitude higher in these mutants compared with wildtype(50, 52).”
From Membrane exporters of fluoride ion (2021) · cites this paper as [50]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
No references could be resolved yet.
Research works printed but not linked: 21
- Accardi, 2010, CLC channels and transporters: proteins with borderline personalities, Biochim. Biophys. Acta., 1798, 1457, 10.1016/j.bbamem.2010.02.022 · DOI
- Accardi, 2006, Synergism between halide binding and proton transport in a CLC-type exchanger, J. Mol. Biol., 362, 691, 10.1016/j.jmb.2006.07.081 · DOI · Paper page
- Baker, 2012, Widespread genetic switches and toxicity resistance proteins for fluoride, Science., 335, 233, 10.1126/science.1215063 · DOI · Paper page
- Cametti, 2009, Recognition and sensing of fluoride anion, Chem. Commun. (Camb.)., 2809, 10.1039/b902069a · DOI · Paper page
- De Stefano, 2013, A single point mutation reveals gating of the human ClC-5 Cl−/H+ antiporter, J. Physiol., 591, 5879, 10.1113/jphysiol.2013.260240 · DOI
- Dutzler, 2003, Gating the selectivity filter in ClC chloride channels, Science., 300, 108, 10.1126/science.1082708 · DOI · Paper page
- Edgar, 2004, MUSCLE: multiple sequence alignment with high accuracy and high throughput, Nucleic Acids Res., 32, 1792, 10.1093/nar/gkh340 · DOI · Paper page
- Finkelstein, 1981, The gramicidin A channel: a review of its permeability characteristics with special reference to the single-file aspect of transport, J. Membr. Biol., 59, 155, 10.1007/BF01875422 · DOI
- Gouy, 2010, SeaView version 4: A multiplatform graphical user interface for sequence alignment and phylogenetic tree building, Mol. Biol. Evol., 27, 221, 10.1093/molbev/msp259 · DOI
- Guindon, 2010, New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of PhyML 3.0, Syst. Biol., 59, 307, 10.1093/sysbio/syq010 · DOI · Paper page
- Jin, 1999, Light scattering characterization of extruded lipid vesicles, Eur. Biophys. J., 28, 187, 10.1007/s002490050199 · DOI
- Li, 2013, Eukaryotic resistance to fluoride toxicity mediated by a widespread family of fluoride export proteins, Proc. Natl. Acad. Sci. USA., 110, 19018, 10.1073/pnas.1310439110 · DOI · Paper page
- Lim, 2013, Fluoride-dependent interruption of the transport cycle of a CLC Cl−/H+ antiporter, Nat. Chem. Biol., 9, 721, 10.1038/nchembio.1336 · DOI · Paper page
- Miller, 2006, ClC chloride channels viewed through a transporter lens, Nature., 440, 484, 10.1038/nature04713 · DOI
- Picollo, 2009, Basis of substrate binding and conservation of selectivity in the CLC family of channels and transporters, Nat. Struct. Mol. Biol., 16, 1294, 10.1038/nsmb.1704 · DOI
- Schultz, 1962, Cation transport in Escherichia coli. II. Intracellular chloride concentration, J. Gen. Physiol., 46, 159, 10.1085/jgp.46.1.159 · DOI · Paper page
- Smith, 2010, Voltage-dependent charge movement associated with activation of the CLC-5 2Cl−/1H+ exchanger, FASEB J., 24, 3696, 10.1096/fj.09-150649 · DOI
- Stockbridge, 2012, Fluoride resistance and transport by riboswitch-controlled CLC antiporters, Proc. Natl. Acad. Sci. USA., 109, 15289, 10.1073/pnas.1210896109 · DOI · Paper page
- Stockbridge, 2013, A family of fluoride-specific ion channels with dual-topology architecture, eLife., 2, e01084, 10.7554/eLife.01084 · DOI · Paper page
- Walden, 2007, Uncoupling and turnover in a Cl−/H+ exchange transporter, J. Gen. Physiol., 129, 317, 10.1085/jgp.200709756 · DOI · Paper page
- Zifarelli, 2007, CLC chloride channels and transporters: a biophysical and physiological perspective, Rev. Physiol. Biochem. Pharmacol., 158, 23, 10.1007/112_2006_0605 · DOI
Cited by
Sorted by citations
Crystal structures of a double-barrelled fluoride ion channel
Stockbridge, R. B., Kolmakova-Partensky, L., Shane, T., Koide, A., Koide, S., Miller, C., & Newstead, S. (2015) · Nature · doi:10.1038/nature14981 · Cited by 119
Self-citationStockbridge, R. B., & Wackett, L. P. (2024) · Nature Communications · doi:10.1038/s41467-024-49018-1 · Cited by 80
Self-citationMembrane exporters of fluoride ion
McIlwain, B. C., Ruprecht, M. T., & Stockbridge, R. B. (2021) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-071520-112507 · Cited by 69
Self-citationHu, M., & Scott, C. (2024) · Applied and Environmental Microbiology · doi:10.1128/aem.00157-24 · Cited by 63
Banerjee, A., Kang, C.-Y., An, M., Koff, B. B., Sunder, S., Kumar, A., Tenuta, L. M. A., & Stockbridge, R. B. (2024) · mBio · doi:10.1128/mbio.00184-24 · Cited by 17
Self-citationEts, L., Ilves, H., Juhe, L., Ilmjärv, T., Puiggené, Ò., Nikel, P. I., & Kivisaar, M. (2026) · Journal of Bacteriology · doi:10.1128/jb.00479-25 · Cited by 1
Metadata
- Authors
- Brammer, A. E., Stockbridge, R. B., & Miller, C.
- Venue
- Journal of General Physiology
- Publisher
- Rockefeller University Press
- Published
- 2014-07-28
- Volume
- 144
- Issue
- 2
- Pages
- 129-136
- ISSN
- 1540-7748
- 0022-1295
- PMC
- PMC4113899
- Cited by
- 54
- References
- 0
- Language
- en
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
