title: On the structural basis of modal gating behavior in K(+) channels.
abstract: Modal-gating shifts represent an effective regulatory mechanism by which ion channels control the extent and time course of ionic fluxes. Under steady-state conditions, the K(+) channel KcsA shows three distinct gating modes, high-P(o), low-P(o) and a high-frequency flicker mode, each with about an order of magnitude difference in their mean open times. Here we show that in the absence of C-type inactivation, mutations at the pore-helix position Glu71 unmask a series of kinetically distinct modes of gating in a side chain-specific way. These gating modes mirror those seen in wild-type channels and suggest that specific interactions in the side chain network surrounding the selectivity filter, in concert with ion occupancy, alter the relative stability of pre-existing conformational states of the pore. The present results highlight the key role of the selectivity filter in regulating modal gating behavior in K(+) channels.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Chicago, Center for Integrative Science, Chicago, Illinois, USA.
authors.forename: Sudha
authors.initials: S
authors.lastname: Chakrapani
authors.forename: Julio F
authors.initials: JF
authors.lastname: Cordero-Morales
authors.forename: Vishwanath
authors.initials: V
authors.lastname: Jogini
authors.forename: Albert C
authors.initials: AC
authors.lastname: Pan
authors.forename: D Marien
authors.initials: DM
authors.lastname: Cortes
authors.forename: Benoît
authors.initials: B
authors.lastname: Roux
authors.forename: Eduardo
authors.initials: E
authors.lastname: Perozo
mesh_terms: D019943:Amino Acid Substitution; D001426:Bacterial Proteins / Q000737:chemistry* / Q000502:physiology; D018360:Crystallography, X-Ray; D015640:Ion Channel Gating; D007700:Kinetics; D008958:Models, Molecular; D009154:Mutation; D015221:Potassium Channels / Q000737:chemistry* / Q000502:physiology; D017434:Protein Structure, Tertiary; D020539:Sequence Analysis, Protein
chemical_list: D001426:Bacterial Proteins; D015221:Potassium Channels; C107790:prokaryotic potassium channel