A single NaK channel conformation is not enough for non-selective ion conduction

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.

Direct knock-on of desolvated ions governs strict ion selectivity in K+ channels

“…These dynamics cause a small widening of the SF on average, and thereby slightly relax the strict geometric constraints for ion transfer, especially at the central ion binding site. Similar findings have recently been reported for the related NaK channel 45 .…”

“…The diminished K + selectivity of the NaK and NaK2CNG channels has previously been associated with the reduced number of SF ion binding sites 38 , the increased hydration level of ions 22,43,44 , for instance seen in the NaK crystal structure 39,40 , and enhanced structural plasticity of the SF 45 . This led to the conclusion that only channels with four consecutive ion binding sites in the SF can ensure fully K + selective ion permeation.…”

Wettability and Applications of Nanochannels

“…However, in the case of the life system, the fast transport of ions and molecules is in the ultrafast fluid state, which is caused by a precisely quantized flow. For example, a K + nanochannel from Streptomyces lividans comprises two K + ions with a distance of 7.5 Å, also with a H 2 O molecule in the middle ( Figure a); the NaK nonselective nanochannel only allows one hydrated Na + ion in the channel, each Ca 2+ channel in calmodulin also simultaneously binds two Ca 2+ ions; and the H 2 O channel allows transport of H 2 O molecules in the way of ordered molecular chain (Figure b), etc. Such phenomena demonstrate that the ultrafast transport conducts in a quantum way with single ionic or molecular chain, so we have proposed a concept of QSF to understand this ultrafast fluid .…”

1D Nanoconfined Ordered‐Assembly Reaction

“…[4] However, the fast mass transport in living systems is in an ultrafast liquid state, which stems from a precisely quantized flow. For example, the K + channel from Streptomyces lividans consists of two K + ions about 0.75 nm apart, with one H 2 O molecule in between (Figure 3a); [42,43] the NaK nonselective channel allows only one hydrated Na + ion in the selectivity filter; [44] each Ca 2+ channel in calmodulin binds two Ca 2+ ions simultaneously. [45] These phenomena demonstrate that the ultrafast mass transport in living systems performs in a quantum way with a single ordered ionic or molecular chain.…”