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Title: Protein interactions central to stabilizing the K[superscript +] channel selectivity filter in a four-sited configuration for selective K[superscript +] permeation

Abstract

The structural and functional conversion of the nonselective NaK channel to a K{sup +} selective channel (NaK2K) allows us to identify two key residues, Tyr and Asp in the filter sequence of TVGYGD, that participate in interactions central to stabilizing the K{sup +} channel selectivity filter. By using protein crystallography and channel electrophysiology, we demonstrate that the K{sup +} channel filter exists as an energetically strained structure and requires these key protein interactions working in concert to hold the filter in the precisely defined four-sited configuration that is essential for selective K{sup +} permeation. Disruption of either interaction, as tested on both the NaK2K and eukaryotic K{sub v}1.6 channels, can reduce or completely abolish K{sup +} selectivity and in some cases may also lead to channel inactivation due to conformational changes at the filter. Additionally, on the scaffold of NaK we recapitulate the protein interactions found in the filter of the Kir channel family, which uses a distinct interaction network to achieve similar stabilization of the filter.

Authors:
; ; ;  [1]
  1. UTSMC
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
NIHOTHERHHMI
OSTI Identifier:
1028508
Resource Type:
Journal Article
Journal Name:
Proc. Natl. Acad. Sci. USA
Additional Journal Information:
Journal Volume: 108; Journal Issue: (40) ; 10, 2011; Journal ID: ISSN 0027-8424
Country of Publication:
United States
Language:
ENGLISH

Citation Formats

Sauer, David B., Zeng, Weizhong, Raghunathan, Srinivasan, and Jiang, Youxing. Protein interactions central to stabilizing the K[superscript +] channel selectivity filter in a four-sited configuration for selective K[superscript +] permeation. United States: N. p., 2019. Web. doi:10.1073/pnas.1111688108.
Sauer, David B., Zeng, Weizhong, Raghunathan, Srinivasan, & Jiang, Youxing. Protein interactions central to stabilizing the K[superscript +] channel selectivity filter in a four-sited configuration for selective K[superscript +] permeation. United States. doi:10.1073/pnas.1111688108.
Sauer, David B., Zeng, Weizhong, Raghunathan, Srinivasan, and Jiang, Youxing. Thu . "Protein interactions central to stabilizing the K[superscript +] channel selectivity filter in a four-sited configuration for selective K[superscript +] permeation". United States. doi:10.1073/pnas.1111688108.
@article{osti_1028508,
title = {Protein interactions central to stabilizing the K[superscript +] channel selectivity filter in a four-sited configuration for selective K[superscript +] permeation},
author = {Sauer, David B. and Zeng, Weizhong and Raghunathan, Srinivasan and Jiang, Youxing},
abstractNote = {The structural and functional conversion of the nonselective NaK channel to a K{sup +} selective channel (NaK2K) allows us to identify two key residues, Tyr and Asp in the filter sequence of TVGYGD, that participate in interactions central to stabilizing the K{sup +} channel selectivity filter. By using protein crystallography and channel electrophysiology, we demonstrate that the K{sup +} channel filter exists as an energetically strained structure and requires these key protein interactions working in concert to hold the filter in the precisely defined four-sited configuration that is essential for selective K{sup +} permeation. Disruption of either interaction, as tested on both the NaK2K and eukaryotic K{sub v}1.6 channels, can reduce or completely abolish K{sup +} selectivity and in some cases may also lead to channel inactivation due to conformational changes at the filter. Additionally, on the scaffold of NaK we recapitulate the protein interactions found in the filter of the Kir channel family, which uses a distinct interaction network to achieve similar stabilization of the filter.},
doi = {10.1073/pnas.1111688108},
journal = {Proc. Natl. Acad. Sci. USA},
issn = {0027-8424},
number = (40) ; 10, 2011,
volume = 108,
place = {United States},
year = {2019},
month = {3}
}

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