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Publication Abstract from PubMed

Fluoride/proton antiporters of the CLC(F) family combat F(-) toxicity in bacteria by exporting this halide from the cytoplasm. These transporters belong to the widespread CLC superfamily but display transport properties different from those of the well-studied Cl(-)/H(+) antiporters. Here, we report a structural and functional investigation of these F(-)-transport proteins. Crystal structures of a CLC(F) homolog from Enterococcus casseliflavus are captured in two conformations with simultaneous accessibility of F(-) and H(+) ions via separate pathways on opposite sides of the membrane. Manipulation of a key glutamate residue critical for H(+) and F(-) transport reverses the anion selectivity of transport; replacement of the glutamate with glutamine or alanine completely inhibits F(-) and H(+) transport while allowing for rapid uncoupled flux of Cl(-). The structural and functional results lead to a 'windmill' model of CLC antiport wherein F (-) and H(+) simultaneously move through separate ion-specific pathways that switch sidedness during the transport cycle.

A CLC-type F(-)/H(+) antiporter in ion-swapped conformations.,Last NB, Stockbridge RB, Wilson AE, Shane T, Kolmakova-Partensky L, Koide A, Koide S, Miller C Nat Struct Mol Biol. 2018 Jun 25. pii: 10.1038/s41594-018-0082-0. doi:, 10.1038/s41594-018-0082-0. PMID:29941917^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.