Figure 1. Substrate-free, Na⁺-bound state is outward-open.

a, Superposition of the outward-open and leucine-bound outward-occluded conformations. Outward-open structure is colored with Na⁺ ions as purple spheres. The outward-occluded structure with Na⁺ ions (spheres) is grey and leucine in stick representation. b, Schematic of scaffold and core domains, EL4, the pivot points of hinge movements in TMs 1 and 6 (solid black circles) and the substrate (S) and sodium sites (+). c, Superposition, as in panel a, illustrating that a ~9° rotation about an axis passing through the middle of the core domain (yellow arrow) describes the conformational change associated with opening to the outside. Pivot points are shown as in panel b. d, Rupture of extracellular gate interactions (grey dashed lines) in the outward-open structure. Two water molecules that bridge Arg 30 and Asp 404 in the outward-occluded state are shown as red spheres. e, Surface representation of the outward-open structure with the zig-zag pink line indicating a closed intracellular pathway. Leucine, where shown, is from the outward-occluded Leu-bound structure.