Fig. 1.
Structure of the alpha subunit of Nav channels. Each alpha subunit folds into 4 domains, each containing 6 transmembrane segments (S1-6). S1-4 segments form the voltage sensing module, and S5-6 with the re-entrant P-loop serve as the pore-forming module. White circles locate the inner ‘DEKA’ ring of amino residues from the 4 domains (D1p50, E2p50, K3p50, and A4p50) that form the narrowest part of the ion selectivity filter among eukaryotic Nav1 channels. The mutation p.Q383E (red) is adjacent to the ‘DEKA’ ring, resulting in an ED-motif (E1p49 and D1p50) in the P-loop of the first domain within the selectivity filter.