Structural mechanism of C-type inactivation in K(+) channels.

Publication Type:

Journal Article


Nature, Volume 466, Issue 7303, p.203-8 (2010)


Bacterial Proteins, Binding Sites, Crystallography, X-Ray, Electrons, Ion Channel Gating, Kinetics, Models, Biological, Models, Molecular, Potassium, Potassium Channels, Protein Conformation, Streptomyces lividans, Structure-Activity Relationship


<p>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.</p>