title: Differential binding of monovalent cations to KcsA: Deciphering the mechanisms of potassium channel selectivity.
abstract: This work explores whether the ion selectivity and permeation properties of a model potassium channel, KcsA, could be explained based on ion binding features. Non-permeant Na+or Li+bind with low affinity (millimolar KD's) to a single set of sites contributed by the S1 and S4 sites seen at the selectivity filter in the KcsA crystal structure. Conversely, permeant K+, Rb+, Tl+and even Cs+bind to two different sets of sites as their concentration increases, consistent with crystallographic evidence on the ability of permeant species to induce concentration-dependent transitions between conformational states (non-conductive and conductive) of the channel's selectivity filter. The first set of such sites, assigned also to the crystallographic S1 and S4 sites, shows similarly high affinities for all permeant species (micromolar KD's), thus, securing displacement of potentially competing non-permeant cations. The second set of sites, available only to permeant cations upon the transition to the conductive filter conformation, shows low affinity (millimolar KD's), thus, favoring cation dissociation and permeation and results from the contribution of all S1 through S4 crystallographic sites. The differences in affinities between permeant and non-permeant cations and the similarities in binding behavior within each of these two groups, correlate fully with their permeabilities relative to K+, suggesting that binding is an important determinant of the channel's ion selectivity. Conversely, the complexity observed in permeation features cannot be explained just in terms of binding and likely relates to reported differences in the occupancy of the S2 and S3 sites by the permeant cations.
authors.affiliation: Instituto de Biología Molecular y Celular, Universidad Miguel Hernández, Elche, 03202 Alicante, Spain.
authors.forename: Estefanía
authors.initials: E
authors.lastname: Montoya
authors.affiliation: Instituto de Biología Molecular y Celular, Universidad Miguel Hernández, Elche, 03202 Alicante, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Lourdes Renart
authors.affiliation: Instituto de Biología Molecular y Celular, Universidad Miguel Hernández, Elche, 03202 Alicante, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Marcela Giudici
authors.affiliation: Instituto de Biología Molecular y Celular, Universidad Miguel Hernández, Elche, 03202 Alicante, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Poveda
authors.affiliation: Instituto de Biología Molecular y Celular, Universidad Miguel Hernández, Elche, 03202 Alicante, Spain.
authors.forename: Asia M
authors.initials: AM
authors.lastname: Fernández
authors.affiliation: Instituto de Biología Molecular y Celular, Universidad Miguel Hernández, Elche, 03202 Alicante, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: Morales
authors.affiliation: Instituto de Biología Molecular y Celular, Universidad Miguel Hernández, Elche, 03202 Alicante, Spain. Electronic address: gonzalez.ros@umh.es.
authors.forename: José M
authors.initials: JM
authors.lastname: González-Ros
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D018360:Crystallography, X-Ray; D008094:Lithium / Q000378:metabolism; D010539:Permeability; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D012964:Sodium / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D015221:Potassium Channels; C107790:prokaryotic potassium channel; D008094:Lithium; D012964:Sodium; D011188:Potassium
keywords: Ion binding; Ion permeability; Ion selectivity; Potassium channel effectors; Protein thermal stability; Selectivity filter conformation