Independent acquisition of sodium selectivity in bacterial and animal sodium channels

Electrical signaling in animal nerves and muscles is largely carried out by proteins in the superfamily of voltage-gated ion channels. These proteins are based on a single homologous domain, but different types exist as single-domain tetramers, two-domain dimers, or four-domain proteins that comprise the whole pore-forming structure. Four-domain channels are hypothesized to have evolved from a single-domain ancestor by two rounds of internal duplication. The role that a channel plays in a cell’s physiology is largely determined by its selectivity for specific ion species and by the stimulus that opens the channel — its method of ‘gating’. The voltage-gated sodium (Nav) and calcium channels (Cav), which drive the upstroke of action potentials and transduce electrical signals into cellular signals, respectively, both have the four-domain architecture, whereas voltage-gated potassium channels (Kv) have only one domain. Crystallographic studies have led to important discoveries about ion pe...