Crystal structures of a double-barrelled fluoride ion channel

To contend with hazards posed by environmental fluoride, microorganisms export this anion through F--specific ion channels of the Fluc family(1-4). Since the recent discovery of Fluc channels, numerous idiosyncratic features of these proteins have been unearthed, including strong selectivity for F- over Cl- and dual-topology dimeric assembly(5,6). To understand the chemical basis for F- permeation and how the antiparallel subunits convene to form a F--selective pore, here we solve the crystal structures of two bacterial Fluc homologues in complex with three different monobody inhibitors, with and without F- present, to a maximum resolution of 2.1 angstrom. The structures reveal a surprising 'double-barrelled' channel architecture in which two F- ion pathways span the membrane, and the dual-topology arrangement includes a centrally coordinated cation, most likely Na+center dot F- selectivity is proposed to arise from the very narrow pores and an unusual anion coordination that exploits the quadrupolar edges of conserved phenylalanine rings.