Department of Molecular Biophysics, Leibniz-Forschungsinstitut für Molekulare Pharmakologie, 13125, Berlin, Germany.
Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, University of Science and Technology of China, 230027, Hefei, P. R. China.
Nat Commun. 2018 Feb 19;9(1):717. doi: 10.1038/s41467-018-03179-y.
NaK and other non-selective channels are able to conduct both sodium (Na) and potassium (K) with equally high efficiency. In contrast to previous crystallographic results, we show that the selectivity filter (SF) of NaK in native-like lipid membranes adopts two distinct conformations that are stabilized by either Na or K ions. The atomic differences of these conformations are resolved by solid-state NMR (ssNMR) spectroscopy and molecular dynamics (MD) simulations. Besides the canonical K permeation pathway, we identify a side entry ion-conduction pathway for Na permeation unique to NaK. Moreover, under otherwise identical conditions ssNMR spectra of the K selective NaK mutant (NaK2K) reveal only a single conformational state. Therefore, we propose that structural plasticity within the SF and the selection of these conformations by different ions are key molecular determinants for highly efficient conduction of different ions in non-selective cation channels.
钠钾通道和其他非选择性通道能够以同样的高效来传导钠离子（Na）和钾离子（K）。与之前的晶体学结果不同，我们发现天然状态下的脂质膜中的钠钾通道的选择性过滤器（SF）采用两种不同的构象，这两种构象分别由钠离子（Na）或钾离子（K）稳定。这些构象的原子差异通过固态核磁共振（ssNMR）光谱和分子动力学（MD）模拟来解析。除了经典的钾离子渗透途径外，我们还鉴定出一种独特的钠离子渗透侧入离子传导途径。此外，在其他相同条件下，钾选择性钠钾通道突变体（NaK2K）的 ssNMR 谱仅显示出单一的构象状态。因此，我们提出选择性过滤器的结构可塑性以及不同离子对这些构象的选择是在非选择性阳离子通道中高效传导不同离子的关键分子决定因素。
