title: Molecular basis of ion permeability in a voltage-gated sodium channel.
abstract: Voltage-gated sodium channels are essential for electrical signalling across cell membranes. They exhibit strong selectivities for sodium ions over other cations, enabling the finely tuned cascade of events associated with action potentials. This paper describes the ion permeability characteristics and the crystal structure of a prokaryotic sodium channel, showing for the first time the detailed locations of sodium ions in the selectivity filter of a sodium channel. Electrostatic calculations based on the structure are consistent with the relative cation permeability ratios (Na(+) ≈ Li(+) ≫ K(+), Ca(2+), Mg(2+)) measured for these channels. In an E178D selectivity filter mutant constructed to have altered ion selectivities, the sodium ion binding site nearest the extracellular side is missing. Unlike potassium ions in potassium channels, the sodium ions in these channels appear to be hydrated and are associated with side chains of the selectivity filter residues, rather than polypeptide backbones.
authors.affiliation: Institute of Structural and Molecular Biology, Birkbeck College University of London, London, UK.
authors.forename: Claire E
authors.initials: CE
authors.lastname: Naylor
authors.affiliation: Institute of Structural and Molecular Biology, Birkbeck College University of London, London, UK.
authors.forename: Claire
authors.initials: C
authors.lastname: Bagnéris
authors.affiliation: Department of Cardiology, Howard Hughes Medical Institute Boston Children's Hospital, Boston, MA, USA Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
authors.forename: Paul G
authors.initials: PG
authors.lastname: DeCaen
authors.affiliation: Institute of Structural and Molecular Biology, Birkbeck College University of London, London, UK.
authors.forename: Altin
authors.initials: A
authors.lastname: Sula
authors.affiliation: Department of Cardiology, Howard Hughes Medical Institute Boston Children's Hospital, Boston, MA, USA Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
authors.forename: Antonella
authors.initials: A
authors.lastname: Scaglione
authors.affiliation: Department of Cardiology, Howard Hughes Medical Institute Boston Children's Hospital, Boston, MA, USA Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Clapham
authors.affiliation: Institute of Structural and Molecular Biology, Birkbeck College University of London, London, UK b.wallace@mail.cryst.bbk.ac.uk.
authors.forename: B A
authors.initials: BA
authors.lastname: Wallace
mesh_terms: D020561:Alphaproteobacteria / Q000737:chemistry; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D002412:Cations / Q000378:metabolism; D018360:Crystallography, X-Ray; D018698:Glutamic Acid / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D015640:Ion Channel Gating; D008958:Models, Molecular; D009154:Mutation; D018408:Patch-Clamp Techniques; D010539:Permeability; D011487:Protein Conformation; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D055672:Static Electricity
chemical_list: D001426:Bacterial Proteins; D002412:Cations; D015222:Sodium Channels; D018698:Glutamic Acid; D012964:Sodium
keywords: crystal structure; electrophysiology; ion permeability; sodium channel