Sodium Ions Do Not Stabilize the Selectivity Filter of a Potassium Channel

被引：10
作者：
Hendriks, Kitty [1 ]
Oester, Carl [1 ]
Shi, Chaowei [1 ,2 ]
Sun, Han [3 ]
Lange, Adam [1 ,4 ]
机构：
[1] Leibniz Forschungsinst Mol Pharmakol, Dept Mol Biophys, Robert Rossle Str 10, D-13125 Berlin, Germany
[2] Univ Sci & Technol China, Sch Life Sci, Hefei Natl Lab Phys Sci Microscale, Huangshan Rd 443, Hefei 230027, Peoples R China
[3] Leibniz Forschungsinst Mol Pharmakol, Struct Chem & Computat Biophys Grp, Robert Rossle Str 10, D-13125 Berlin, Germany
[4] Humboldt Univ, Inst Biol, Invalidenstr 42, D-10115 Berlin, Germany
来源：
JOURNAL OF MOLECULAR BIOLOGY | 2021年 / 433卷 / 15期
关键词：
membrane proteins; ion channels; ion selectivity; NMR; protein dynamics; LONG-QT SYNDROME; K+ CHANNEL; KCSA; BINDING; MECHANISM; STATE; PERMEATION; DYNAMICS;
D O I：
10.1016/j.jmb.2021.167091
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Ion conduction is an essential function for electrical activity in all organisms. The non-selective ion channel NaK was previously shown to adopt two stable conformations of the selectivity filter. Here, we present solid-state NMR measurements of NaK demonstrating a population shift between these conformations induced by changing the ions in the sample while the overall structure of NaK is not affected. We show that two K+-selective mutants (NaK2K and NaK2K-Y66F) suffer a complete loss of selectivity filter stability under Na+ conditions, but do not collapse into a defined structure. Widespread chemical shift perturbations are seen between the Na+ and K+ states of the K+-selective mutants in the region of the pore helix indicating structural changes. We conclude that the stronger link between the selectivity filter and the pore helix in the K+-selective mutants, compared to the non-selective wild-type NaK channel, reduces the ion-dependent conformational flexibility of the selectivity filter. (C) 2021 Elsevier Ltd. All rights reserved.
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页数：11
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