Fig. 1: Cryo-EM structure of full-length hNav1.5 in the intermediate open state.
a Cryo-EM map viewed from the membrane plane. Individual domains, inter-domain linkers, and detergent micelles are segmented and color-coded. b Ribbon model of hNav1.5 viewed from the membrane plane, with a glycol-diosgenin (GDN, gray) molecule at the AG. N-acetylglucosamine (NAG, gray) moieties are shown as sticks. All domains and interdomain linkers are segmented and color-coded according to the density map. c Structural superimposition of hNav1.5 with Nav1.5-E1784K (PDB ID: 7DTC, transparent teal) shows a lateral dilation of the overall structure. The arrangement of VSDI-IV is shown. The density of GDN is highlighted. d Comparison of S4 segments and associated gating charges (GCs) residues across VSDI-IV between hNav1.5 and Nav1.5-E1784K by superimposing each VSD over its S2 segment. GC residues are depicted as sticks. An1 and An2 denote anion1 and anion2, respectively. OR denotes the occluding residue. e Cryo-EM densities of SF and IFM motif residues. f Cryo-EM densities of the π-helical regions in segments S6I and S6III. g Ribbon representation illustrating π-bulging in segments S6I and S6III. Segments S6II and S6IV remain in α-helical conformations. Residues involved in π-bulging are labeled.
