Extended Data Fig. 7: Structural comparison of DAT at outward-facing and occluded conformational states.

a, Structural comparisons between hDAT^DA (violet) and hDAT^MPH (green). TM1a, TM1b, and TM10 of hDAT^DA and hDAT^MPH are depicted as cartoons, while other transmembrane helices are shown as cylinders. Residues involve in the interaction between TM1b and TM10 are illustrated as sticks, and the interaction region is outlined in a dashed box. b-c, Enlarged view of the interactions of TM1b and TM10 of hDAT^DA in the occluded (b) and outward-facing (c) conformations. Key residues and interactions are represented by sticks and dashed lines, respectively. The distances of Cα between the D476 and R85 are indicated by dashed lines and labeled. d, Cryo-EM density and model of the sodium and chloride binding pocket. e-f, Analysis of Na1 (e), Na2 (f), and Cl (e) coordination in hDAT^MPH. The key residues for interaction are presented as sticks and labeled. g, Analysis of Na1, Na2, and Cl coordination in hDAT and dDAT. The key residues for interaction are presented as sticks and labeled. h, Comparison of the binding sites of Na1, Na2, and Cl between hDAT^DA and hDAT^MPH. TM1 and TM6 are shown as cartoons. The changes are labeled by red arrows. i-k, Expanded comparison view of the binding sites of Na1 (i), Na2 (j), and Cl (k) between hDAT^DA and hDAT^MPH.