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Nature. 2010 Jul 8;466(7303):203-8. doi: 10.1038/nature09153.

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

Author information

1
Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, University of Chicago, Illinois 60637, USA.

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.

PMID:
20613835
PMCID:
PMC3033749
DOI:
10.1038/nature09153
[Indexed for MEDLINE]
Free PMC Article

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