Structural mechanism of C-type inactivation in K[superscript +] channels

Journal Article · Mon Aug 30 04:00:00 EDT 2010 · Nature

DOI:https://doi.org/10.1038/nature09153· OSTI ID:1002558

Cuello, Luis G; Jogini, Vishwanath; Cortes, D Marien; Perozo, Eduardo ^[1]

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1. UC

Interconversion between conductive and non-conductive forms of the K{sup +} 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{sup +} 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 {angstrom} in closed KcsA (C{alpha}-C{alpha} distances at Thr112) to 32 {angstrom} 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{sup +} channels.

• Research Organization: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
• Sponsoring Organization: USDOE
• OSTI ID: 1002558
• Journal Information: Nature, Journal Name: Nature Journal Issue: 07, 2010 Vol. 466
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

36 MATERIALS SCIENCE
CRYSTAL STRUCTURE
INACTIVATION
OPENINGS
STREPTOMYCES