Fig. 3

Comparison of the HDX of hSERT in the presence of Na⁺ and 5-HT with Na⁺. a A difference plot illustrating the difference in HDX between the Na⁺ and 5-HT states for the 62 peptides identified from hSERT over the measured time points (orange—0.25 min; red—1 min; cyan—10 min; green—1 h; black—8 h). Positive and negative values indicate decreased or increased HDX, respectively, when hSERT is in the presence of 5-HT and Na⁺ compared to Na⁺ only. The peptides are arranged according to their position from the N- to C-terminal (Supplementary Table 1). The dotted line (±0.35D) indicates 95% CI as a threshold for significance. Structural motifs in hSERT are indicated along the x-axis above the plot. b, c Regions showing significant increase (red) or decrease (blue) in dynamics (i.e., HDX) in the presence of 5-HT and Na⁺ compared to Na⁺ alone are plotted on the crystal structure (PDB ID: 5i75) (b) and a snake diagram (c) of hSERT. Regions coloured grey indicate insignificant difference in HDX between the two experimental states (light grey) or regions not covered by peptides (dark grey). Regions showing significant difference in HDX are indicated with black text with residue location in the structural model. Structural elements located on the front side of the crystal structure but do not show significant difference in HDX, are indicated with grey text without residue information for orientation and regions not resolved or truncated in the crystal structure are indicated as dotted lines. Black solid lines at the top and bottom of the structural model show an approximation of the extracellular (Ex.) and intracellular (Int.) boundaries of the membrane, respectively. Source data for the HDX data are provided as a Source data file