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. 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.
Department of Biochemistry, Howard Hughes Medical Institute, Brandeis University, Waltham, Massachusetts 02454, USA.
Randy B
RB
Stockbridge
Department of Biochemistry, Howard Hughes Medical Institute, Brandeis University, Waltham, Massachusetts 02454, USA.
Ludmila
L
Kolmakova-Partensky
Department of Biochemistry, Howard Hughes Medical Institute, Brandeis University, Waltham, Massachusetts 02454, USA.
Tania
T
Shane
Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois 60637, USA.
Akiko
A
Koide
Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois 60637, USA.
Shohei
S
Koide
Department of Biochemistry, Howard Hughes Medical Institute, Brandeis University, Waltham, Massachusetts 02454, USA.|Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford OX1 3QU, UK.
Christopher
C
Miller
Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
Simon
S
Newstead
D000838:Anions / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D018360:Crystallography, X-Ray; D005459:Fluorides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D007473:Ion Channels / Q000737:chemistry* / Q000378:metabolism*; D008954:Models, Biological; D008958:Models, Molecular; D010649:Phenylalanine / Q000378:metabolism; D011487:Protein Conformation
D000838:Anions; D001426:Bacterial Proteins; D007473:Ion Channels; D010649:Phenylalanine; D005459:Fluorides