title: Role of protein dynamics in ion selectivity and allosteric coupling in the NaK channel.
abstract: Flux-dependent inactivation that arises from functional coupling between the inner gate and the selectivity filter is widespread in ion channels. The structural basis of this coupling has only been well characterized in KcsA. Here we present NMR data demonstrating structural and dynamic coupling between the selectivity filter and intracellular constriction point in the bacterial nonselective cation channel, NaK. This transmembrane allosteric communication must be structurally different from KcsA because the NaK selectivity filter does not collapse under low-cation conditions. Comparison of NMR spectra of the nonselective NaK and potassium-selective NaK2K indicates that the number of ion binding sites in the selectivity filter shifts the equilibrium distribution of structural states throughout the channel. This finding was unexpected given the nearly identical crystal structure of NaK and NaK2K outside the immediate vicinity of the selectivity filter. Our results highlight the tight structural and dynamic coupling between the selectivity filter and the channel scaffold, which has significant implications for channel function. NaK offers a distinct model to study the physiologically essential connection between ion conduction and channel gating.
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110;
authors.forename: Joshua B
authors.initials: JB
authors.lastname: Brettmann
authors.affiliation: Department of Biomedical Engineering, Washington University in Saint Louis, St. Louis, MO 63130;
authors.forename: Darya
authors.initials: D
authors.lastname: Urusova
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706.
authors.forename: Marco
authors.initials: M
authors.lastname: Tonelli
authors.affiliation: Department of Biomedical Engineering, Washington University in Saint Louis, St. Louis, MO 63130;
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Silva
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706 henzlerwildm@wisc.edu.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Henzler-Wildman
mesh_terms: D000494:Allosteric Regulation; D001409:Bacillus cereus / Q000737:chemistry*; D018360:Crystallography, X-Ray; D015640:Ion Channel Gating; D007477:Ions; D009682:Magnetic Resonance Spectroscopy; D050505:Mutant Proteins / Q000737:chemistry; D017354:Point Mutation; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012996:Solutions; D013696:Temperature; D013997:Time Factors
chemical_list: D007477:Ions; D050505:Mutant Proteins; D015221:Potassium Channels; D012996:Solutions; D011188:Potassium
keywords: ion channels; membrane protein; protein dynamics; solution NMR