Mechanism for Selectivity-inactivation Coupling in KcsA Potassium Channels
Abstract
Structures of the prokaryotic K{sup +} channel, KcsA, highlight the role of the selectivity filter carbonyls from the GYG signature sequence in determining a highly selective pore, but channels displaying this sequence vary widely in their cation selectivity. Furthermore, variable selectivity can be found within the same channel during a process called C-type inactivation. We investigated the mechanism for changes in selectivity associated with inactivation in a model K{sup +} channel, KcsA. We found that E71A, a noninactivating KcsA mutant in which a hydrogen-bond behind the selectivity filter is disrupted, also displays decreased K{sup +} selectivity. In E71A channels, Na{sup +} permeates at higher rates as seen with {sup 86}Rb{sup +} and {sup 22}Na{sup +} flux measurements and analysis of intracellular Na{sup +} block. Crystal structures of E71A reveal that the selectivity filter no longer assumes the 'collapsed,' presumed inactivated, conformation in low K{sup +}, but a 'flipped' conformation, that is also observed in high K{sup +}, high Na{sup +}, and even Na{sup +} only conditions. The data reveal the importance of the E71-D80 interaction in both favoring inactivation and maintaining high K{sup +} selectivity. We propose a molecular mechanism by which inactivation and K{sup +} selectivity are linked, amore »
- Authors:
- Publication Date:
- Research Org.:
- Brookhaven National Lab. (BNL), Upton, NY (United States)
- Sponsoring Org.:
- USDOE SC OFFICE OF SCIENCE (SC)
- OSTI Identifier:
- 1041664
- Report Number(s):
- BNL-97342-2012-JA
Journal ID: ISSN 0027-8424; PNASA6; TRN: US201212%%82
- DOE Contract Number:
- DE-AC02-98CH10886
- Resource Type:
- Journal Article
- Journal Name:
- Proceedings of the National Academy of Sciences of the United States of America
- Additional Journal Information:
- Journal Volume: 108; Journal Issue: 13; Journal ID: ISSN 0027-8424
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; CARBONYLS; CATIONS; CRYSTAL STRUCTURE; INACTIVATION; MUTANTS; POTASSIUM
Citation Formats
Cheng, W, McCoy, J, Thompson, A, Nichols, C, and Nimigean, C. Mechanism for Selectivity-inactivation Coupling in KcsA Potassium Channels. United States: N. p., 2011.
Web. doi:10.1073/pnas.1014186108.
Cheng, W, McCoy, J, Thompson, A, Nichols, C, & Nimigean, C. Mechanism for Selectivity-inactivation Coupling in KcsA Potassium Channels. United States. https://doi.org/10.1073/pnas.1014186108
Cheng, W, McCoy, J, Thompson, A, Nichols, C, and Nimigean, C. 2011.
"Mechanism for Selectivity-inactivation Coupling in KcsA Potassium Channels". United States. https://doi.org/10.1073/pnas.1014186108.
@article{osti_1041664,
title = {Mechanism for Selectivity-inactivation Coupling in KcsA Potassium Channels},
author = {Cheng, W and McCoy, J and Thompson, A and Nichols, C and Nimigean, C},
abstractNote = {Structures of the prokaryotic K{sup +} channel, KcsA, highlight the role of the selectivity filter carbonyls from the GYG signature sequence in determining a highly selective pore, but channels displaying this sequence vary widely in their cation selectivity. Furthermore, variable selectivity can be found within the same channel during a process called C-type inactivation. We investigated the mechanism for changes in selectivity associated with inactivation in a model K{sup +} channel, KcsA. We found that E71A, a noninactivating KcsA mutant in which a hydrogen-bond behind the selectivity filter is disrupted, also displays decreased K{sup +} selectivity. In E71A channels, Na{sup +} permeates at higher rates as seen with {sup 86}Rb{sup +} and {sup 22}Na{sup +} flux measurements and analysis of intracellular Na{sup +} block. Crystal structures of E71A reveal that the selectivity filter no longer assumes the 'collapsed,' presumed inactivated, conformation in low K{sup +}, but a 'flipped' conformation, that is also observed in high K{sup +}, high Na{sup +}, and even Na{sup +} only conditions. The data reveal the importance of the E71-D80 interaction in both favoring inactivation and maintaining high K{sup +} selectivity. We propose a molecular mechanism by which inactivation and K{sup +} selectivity are linked, a mechanism that may also be at work in other channels containing the canonical GYG signature sequence.},
doi = {10.1073/pnas.1014186108},
url = {https://www.osti.gov/biblio/1041664},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
issn = {0027-8424},
number = 13,
volume = 108,
place = {United States},
year = {Sat Dec 31 00:00:00 EST 2011},
month = {Sat Dec 31 00:00:00 EST 2011}
}