title: 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 CLC(F) 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 CLC(F)s and canonical Cl(-)-transporting CLCs within regions that, in the canonical CLCs, coordinate Cl(-) ion and govern anion transport. A phylogenetic split within the CLC(F) clade, manifested in sequence divergence in the vicinity of this ion-binding center, raises the possibility that these two CLC(F) subclades might exhibit differences in anion selectivity. Several CLC(F) 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 CLC(F)s. 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.
authors: Department of Biochemistry and Howard Hughes Medical Institute, Brandeis University, Waltham, MA 02453Department of Biochemistry and Howard Hughes Medical Institute, Brandeis University, Waltham, MA 02453.
authors: Ashley E
authors: AE
authors: Brammer
authors: Department of Biochemistry and Howard Hughes Medical Institute, Brandeis University, Waltham, MA 02453Department of Biochemistry and Howard Hughes Medical Institute, Brandeis University, Waltham, MA 02453.
authors: Randy B
authors: RB
authors: Stockbridge
authors: Department of Biochemistry and Howard Hughes Medical Institute, Brandeis University, Waltham, MA 02453Department of Biochemistry and Howard Hughes Medical Institute, Brandeis University, Waltham, MA 02453 cmiller@brandeis.edu.
authors: Christopher
authors: C
authors: Miller
mesh_terms: D017920:Antiporters / Q000235:genetics / Q000378:metabolism*; D018118:Chloride Channels / Q000378:metabolism; D002713:Chlorine / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005461:Fluorine / Q000378:metabolism*; D017136:Ion Transport / Q000235:genetics; D009154:Mutation / Q000235:genetics; D010802:Phylogeny; D011487:Protein Conformation; D017494:Proton Pumps / Q000378:metabolism
chemical_list: D017920:Antiporters; D018118:Chloride Channels; D017494:Proton Pumps; D005461:Fluorine; D002713:Chlorine