Fig. 2: Structure of SERT-Fab with vilazodone bound in the S1 site.

a Cryo-EM density (2.78 Å overall resolution) of SERT (purple) in complex with the Fab 15B8 fragment (yellow). Estimated positions of membrane phospholipids surrounding SERT are illustrated by black lines. b The fitted structure of SERT-Fab (purple tube helices) and turned 180° (right). Vilazodone (red spheres) was modeled into a non-protein electron density in the S1 site. c The fitted SERT structure (purple) shown at 30% transparency, marking the electron density of vilazodone (red). d Left: Top-view of vilazodone (red sticks) binding site with depicted stabilizing side chain and backbone residues (purple). The electron density for fitting vilazodone is shown as black mesh. Right: Zoomed-in view with distances shown as dashed lines. e Left: Side-view of vilazodone binding with SERT stabilizing residues. The S2 site is faded in the background. Right: Zoomed-in view of the S1-binding (indole) group of vilazodone. f, g Superimposition of the vilazodone complexes in the presence of imipramine (PDB ID: 7LWD, yellow) and the structure solved herein (red). The constellation of centrally interacting side chain residues shown in dark blue and purple respectively.