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Nature. 2015 Sep 24;525(7570):548-51. doi: 10.1038/nature14981. Epub 2015 Sep 7.

Crystal structures of a double-barrelled fluoride ion channel.

Author information

1
Department of Biochemistry, Howard Hughes Medical Institute, Brandeis University, Waltham, Massachusetts 02454, USA.
2
Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois 60637, USA.
3
Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford OX1 3QU, UK.
4
Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.

Abstract

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.

PMID:
26344196
PMCID:
PMC4876929
DOI:
10.1038/nature14981
[Indexed for MEDLINE]
Free PMC Article
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