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

Abstract

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.

Authors:
; ; ;  [1]
  1. UC
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
USDOE
OSTI Identifier:
1002558
Resource Type:
Journal Article
Journal Name:
Nature
Additional Journal Information:
Journal Volume: 466; Journal Issue: 07, 2010
Country of Publication:
United States
Language:
ENGLISH
Subject:
36 MATERIALS SCIENCE; CRYSTAL STRUCTURE; INACTIVATION; OPENINGS; STREPTOMYCES

Citation Formats

Cuello, Luis G, Jogini, Vishwanath, Cortes, D Marien, and Perozo, Eduardo. Structural mechanism of C-type inactivation in K[superscript +] channels. United States: N. p., 2010. Web. doi:10.1038/nature09153.
Cuello, Luis G, Jogini, Vishwanath, Cortes, D Marien, & Perozo, Eduardo. Structural mechanism of C-type inactivation in K[superscript +] channels. United States. https://doi.org/10.1038/nature09153
Cuello, Luis G, Jogini, Vishwanath, Cortes, D Marien, and Perozo, Eduardo. 2010. "Structural mechanism of C-type inactivation in K[superscript +] channels". United States. https://doi.org/10.1038/nature09153.
@article{osti_1002558,
title = {Structural mechanism of C-type inactivation in K[superscript +] channels},
author = {Cuello, Luis G and Jogini, Vishwanath and Cortes, D Marien and Perozo, Eduardo},
abstractNote = {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.},
doi = {10.1038/nature09153},
url = {https://www.osti.gov/biblio/1002558}, journal = {Nature},
number = 07, 2010,
volume = 466,
place = {United States},
year = {Mon Aug 30 00:00:00 EDT 2010},
month = {Mon Aug 30 00:00:00 EDT 2010}
}