Extended Data Fig. 4: The binding and transport of NE and DA in NET.

a, Extracellular gate in NET. Water molecules are depicted as cyan spheres. Arg81 and Phe317 are key residues in the extracellular gate. Arg81 forms a cation-π interaction with Phe317, as indicated by the black dashed line. Arg81 is also coordinated by Gln314, Asp475, and surrounding water molecules. Hydrogen bonds are represented by cyan dashed lines. b, The extracellular gating residues in outward-open DA-bound dDAT. The cation-π interaction between Phe319 and Arg52 (corresponding to Phe317 and Arg81 in NET) and the salt bridge between Asp475 and Arg52 (corresponding to Asp473 and Arg81 in NET) is disrupted. c-d, Similar binding mode of NE and DA in the central substrate binding pocket of NET. DA and NE adopt similar orientations in the central pocket. The β-hydroxyl group of NE faces to the opening tunnel without coordination. e, Determination of the kinetic parameters of NET for the transport of NE and DA. The data were fitted using the Michaelis–Menten non-linear fitting method. Curves were calculated from n = 3 biologically independent experiments.