Secondary chelation through shared water provides ion selectivity in bacterial sodium channels

Selective ion conductance through sodium channels has been intensely investigated for decades. Here, we focus on the sodium and potassium hydration shell structure and propose the mechanism of Na⁺ over K⁺ selectivity in the bacterial sodium channel Na_vMs. We suggest that the channel selectivity filter forms hydrogen bonds with Na⁺ hydration shell in a perfect octahedral stereometry, which mimics bulk water and provides high Na⁺ conductance. Using molecular dynamics simulations, we reveal a conserved ion-binding site formed by carboxyl/carbonyl groups, where both Na⁺ and K⁺ remain fully hydrated. While passing through the selectivity filter, Na⁺ octahedral shell remains unhindered, while K⁺ square antiprismatic shell is squeezed, creating an energy barrier for K⁺ current. In contrast to K⁺-channels, where the selectivity filter interacts with the permeating ions directly ("primary" chelation), Na_vMs gropes the ion hydration shell, performing "secondary" chelation. This ion recognition mechanism is probably widespread in other channels and pores.