Abstract
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.
Highlights
NaK and other non-selective channels are able to conduct both sodium (Na+) and potassium (K+) with high efficiency
No structural rearrangement was observed in the crystal structures of NaK with Na+, K+, or rubidium (Rb+) and a single selectivity filter (SF) conformation was detected for NaK in bicelles at high temperature by solution-state NMR15
We use a combination of solid-state NMR (ssNMR) and advanced molecular dynamics (MD) simulations to investigate the detailed mechanism of ion non-selectivity in the NaK channel
Summary
NaK and other non-selective channels are able to conduct both sodium (Na+) and potassium (K+) with high efficiency. We use a combination of ssNMR and advanced molecular dynamics (MD) simulations to investigate the detailed mechanism of ion non-selectivity in the NaK channel. Single-channel conductance measurements verified that NaK in our lipid bilayer preparation is functional (Supplementary Fig. 1).
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