title: Structural mechanism of C-type inactivation in K(+) channels.
abstract: Interconversion between conductive and non-conductive forms of the K(+) channel selectivity filter underlies a variety of gating events, from flicker transitions (at the microsecond timescale) to C-type inactivation (millisecond to second timescale). Here we report the crystal structure of the Streptomyces lividans K(+) channel KcsA in its open-inactivated conformation and investigate the mechanism of C-type inactivation gating at the selectivity filter from channels 'trapped' in a series of partially open conformations. Five conformer classes were identified with openings ranging from 12 A in closed KcsA (Calpha-Calpha distances at Thr 112) to 32 A when fully open. They revealed a remarkable correlation between the degree of gate opening and the conformation and ion occupancy of the selectivity filter. We show that a gradual filter backbone reorientation leads first to a loss of the S2 ion binding site and a subsequent loss of the S3 binding site, presumably abrogating ion conduction. These structures indicate a molecular basis for C-type inactivation in K(+) channels.
authors.affiliation: Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, University of Chicago, Illinois 60637, USA.
authors.forename: Luis G
authors.initials: LG
authors.lastname: Cuello
authors.forename: Vishwanath
authors.initials: V
authors.lastname: Jogini
authors.forename: D Marien
authors.initials: DM
authors.lastname: Cortes
authors.forename: Eduardo
authors.initials: E
authors.lastname: Perozo
mesh_terms: D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004583:Electrons; D015640:Ion Channel Gating; D007700:Kinetics; D008954:Models, Biological; D008958:Models, Molecular; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D048170:Streptomyces lividans / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D001426:Bacterial Proteins; D015221:Potassium Channels; C107790:prokaryotic potassium channel; D011188:Potassium