Potassium (K+) channels are membrane proteins with the remarkable ability to very selectively conduct K+ ions across the membrane. High-resolution structures have revealed that dehydrated K+ ions permeate through the narrowest region of the pore, formed by the backbone carbonyls of the signature selectivity filter (SF) sequence TxGYG. However, the existence of nonselective channels with similar SF sequences, as well as effects of mutations in other regions on selectivity, suggest that the SF is not the sole determinant of selectivity. We changed the selectivity of the KirBac1.1 channel by introducing mutations at residue I131 in transmembrane helix 2 (TM2). These mutations increase Na+ flux in the absence of K+ and introduce significant proton conductance. Consistent with K+ channel crystal structures, single-molecule FRET experiments show that the SF is conformationally constrained and stable in high-K+ conditions but undergoes transitions to dilated low-FRET states in high-Na+/low-K+ conditions. Relative to wild-type channels, I131M mutants exhibit marked shifts in the K+ and Na+ dependence of SF dynamics to higher K+ and lower Na+ concentrations. These results illuminate the role of I131, and potentially other structural elements outside the SF, in controlling ion selectivity, by suggesting that the physical interaction of these elements with the SF contributes to the relative stability of the constrained K+-induced SF configuration versus nonselective dilated conformations.
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March 29 2021
Pore-forming transmembrane domains control ion selectivity and selectivity filter conformation in the KirBac1.1 potassium channel
Marcos Matamoros
,
Marcos Matamoros
Center for Investigation of Membrane Excitability Diseases, and Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO
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Colin G. Nichols
Center for Investigation of Membrane Excitability Diseases, and Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO
Correspondence to Colin G. Nichols: cnichols@wustl.edu
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Marcos Matamoros
Center for Investigation of Membrane Excitability Diseases, and Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO
Colin G. Nichols
Center for Investigation of Membrane Excitability Diseases, and Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO
Correspondence to Colin G. Nichols: cnichols@wustl.edu
Received:
June 18 2020
Revision Received:
November 23 2020
Accepted:
March 09 2021
Online Issn: 1540-7748
Print Issn: 0022-1295
© 2021 Matamoros and Nichols
2021
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
J Gen Physiol (2021) 153 (5): e202012683.
Article history
Received:
June 18 2020
Revision Received:
November 23 2020
Accepted:
March 09 2021
Citation
Marcos Matamoros, Colin G. Nichols; Pore-forming transmembrane domains control ion selectivity and selectivity filter conformation in the KirBac1.1 potassium channel. J Gen Physiol 3 May 2021; 153 (5): e202012683. doi: https://doi.org/10.1085/jgp.202012683
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