Crystal structures of a double-barrelled fluoride ion channel

By R. Stockbridge, L. Kolmakova-Partensky, T. Shane, A. Koide, S. Koide, Christopher Miller, S. Newstead. 2015

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To contend with hazards posed by environmental fluoride, microorganisms export this anion through F−-specific ion channels of the Fluc family. 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. 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 Å. 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+. 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.

Subfields: Inorganic Chemistry, Materials Chemistry, Pharmaceutical Science