Crystal structures of a double-barrelled fluoride ion channel

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anions / chemistry
  • Anions / metabolism
  • Anions / pharmacology
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / metabolism*
  • Cell Membrane / metabolism
  • Crystallography, X-Ray
  • Fluorides / chemistry
  • Fluorides / metabolism*
  • Fluorides / pharmacology*
  • Ion Channels / chemistry*
  • Ion Channels / metabolism*
  • Models, Biological
  • Models, Molecular
  • Phenylalanine / metabolism
  • Protein Conformation


  • Anions
  • Bacterial Proteins
  • Ion Channels
  • Phenylalanine
  • Fluorides

Associated data

  • PDB/5A40
  • PDB/5A41
  • PDB/5A43