title: Ion binding affinity in the cavity of the KcsA potassium channel.
abstract: The hydrophobic cell membrane interior presents a large energy barrier for ions to permeate. Potassium channels reduce this barrier by creating a water-filled cavity at the middle of their ion conduction pore to allow ion hydration and by directing the C-terminal "end charge" of four alpha-helices toward the water-filled cavity. Here we have studied the interaction of monovalent cations with the cavity of the KcsA K(+) channel using X-ray crystallography. In these studies, Tl(+) was used as an analogue for K(+) and the total ion-stabilization energy for Tl(+) in the cavity was estimated by measuring its binding affinity. Binding affinity for the Na(+) ion was also measured, revealing a weak selectivity ( approximately 7-fold) favoring Tl(+) over Na(+). The structures of the cavity containing Na(+), K(+), Tl(+), Rb(+), and Cs(+) are compared. These results are consistent with a fairly large (more negative than -100 mV) electrostatic potential inside the cavity, and they also imply the presence of a weak nonelectrostatic component to a cation's interaction with the cavity.
authors.affiliation: Howard Hughes Medical Institute and Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, 1230 York Avenue, New York, New York 10021, USA.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Zhou
authors.forename: Roderick
authors.initials: R
authors.lastname: MacKinnon
mesh_terms: D002462:Cell Membrane / Q000737:chemistry; D002586:Cesium / Q000378:metabolism; D018360:Crystallography, X-Ray; D005583:Fourier Analysis; D057927:Hydrophobic and Hydrophilic Interactions; D007477:Ions / Q000378:metabolism*; D009994:Osmolar Concentration; D011188:Potassium / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000737:chemistry / Q000378:metabolism*; D017433:Protein Structure, Secondary; D012413:Rubidium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D055672:Static Electricity; D013793:Thallium / Q000378:metabolism
chemical_list: D007477:Ions; D024661:Potassium Channels, Inwardly Rectifying; D002586:Cesium; D012964:Sodium; D013793:Thallium; D012413:Rubidium; D011188:Potassium