title: Tuning the ion selectivity of tetrameric cation channels by changing the number of ion binding sites.
abstract: Selective ion conduction across ion channel pores is central to cellular physiology. To understand the underlying principles of ion selectivity in tetrameric cation channels, we engineered a set of cation channel pores based on the nonselective NaK channel and determined their structures to high resolution. These structures showcase an ensemble of selectivity filters with a various number of contiguous ion binding sites ranging from 2 to 4, with each individual site maintaining a geometry and ligand environment virtually identical to that of equivalent sites in K(+) channel selectivity filters. Combined with single channel electrophysiology, we show that only the channel with four ion binding sites is K(+) selective, whereas those with two or three are nonselective and permeate Na(+) and K(+) equally well. These observations strongly suggest that the number of contiguous ion binding sites in a single file is the key determinant of the channel's selectivity properties and the presence of four sites in K(+) channels is essential for highly selective and efficient permeation of K(+) ions.
authors.affiliation: Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9040, USA.
authors.forename: Mehabaw G
authors.initials: MG
authors.lastname: Derebe
authors.forename: David B
authors.initials: DB
authors.lastname: Sauer
authors.forename: Weizhong
authors.initials: W
authors.lastname: Zeng
authors.forename: Amer
authors.initials: A
authors.lastname: Alam
authors.forename: Ning
authors.initials: N
authors.lastname: Shi
authors.forename: Youxing
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D001412:Bacillus subtilis / Q000378:metabolism; D001665:Binding Sites; D002244:Carbon / Q000737:chemistry; D018360:Crystallography, X-Ray / Q000379:methods; D004594:Electrophysiology / Q000379:methods; D007477:Ions / Q000737:chemistry*; D008024:Ligands; D009154:Mutation; D010100:Oxygen / Q000737:chemistry; D011188:Potassium / Q000737:chemistry; D015221:Potassium Channels / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D012964:Sodium / Q000737:chemistry
chemical_list: D007477:Ions; D008024:Ligands; D015221:Potassium Channels; D002244:Carbon; D012964:Sodium; D011188:Potassium; D010100:Oxygen