Fig. 3: Structural transitions show gating rearrangements and dual function helices.

a Structural superposition of the inward-facing and occluded conformations. The TMs of the inward-facing (IFS) structure are coloured red and light blue, while the TMs of the occluded structure are coloured orange and light purple. The N-terminal bundle is coloured blue/purple and the C-terminal bundle is coloured orange/red. Dashed boxes correspond to views in panels (b–d). b Intracellular gate interactions. In the IFS (top), a charge network is observed in the N-terminal bundle, and in the occluded conformation (bottom), R459 (TM11) interacts with this network. c Gating interactions at the intracellular helix (ICH) domain where a salt bridge forms between R282 and D519 in the occluded conformation. Red asterisks indicate positions of variants associated with SPCD. d Extracellular gate interactions, where Y482 and D139 H-bond in the IFS (top) and move further apart in the occluded conformation (bottom). Cryo-EM density for residues detailed in (b–d) is shown in Supplementary Fig. 5. e Residues on TM1 (purple) and TM7 (brown) form a hydrophobic extracellular gate above the carnitine-binding site. As well as gating, residues on TM1 form the Na^+-binding site. The PNGFxG motif observed in the Na⁺-dependent hOCTN2, hOCTN1 and mOCTN3 is indicated. Proline and glycine residues are coloured grey. f Flexibility of TM11 (orange) and formation of a hydrogen-bonding network with TM2 (blue) in the occluded carnitine-bound structure. Arrows and transparent overlay illustrates TM11 bending during the inward-occluded conformational change. The position of the conserved G473/P478 motif is indicated.