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. Author manuscript; available in PMC: 2020 Dec 15.
Published in final edited form as: Neuropharmacology. 2019 Jun 20;161:107676. doi: 10.1016/j.neuropharm.2019.107676

Fig. 4. Extracellular loop segment EL2b is distinguished by its propensity to make interfacial contacts specific to hDAT.

Fig. 4

(A) The diagrams display (in vdW spheres) the EL2b residues that make intersubunit contacts in trimer models generated for DAT (left) and SERT (right), consistent with the trimer-W238 presented in Fig 1A–B. A protomer is shown for each transporter in tube representation. Hydrophobic, hydrophilic, acidic and basic residues are colored in white, green, red, and blue. (B) Multiple sequence alignment of human and fruit fly DATs (hDAT and dDAT), human SERT, NET, glycine transporter (Gly1) and GABA transporter (GAT1). (C). Comparison of residue fluctuation profiles for SERT, DAT and LeuT (labelled) in OF (solid) or IF (dashed) states, computed using the ANM. Curves are vertically shifted for clarity and represent the probability distributions of mean-square fluctuations of residues. Selected residues are indicated by arrows and dashed lines. EL2 exhibits transporter-specific fluctuations. (D) Cross-correlations between residue fluctuations averaged over the ensemble of transporters listed in Table S3. The map represents the signature dynamics of the shared fold, obtained by SignDy (Zhang et al., 2019). The region corresponding to the cross-correlations of EL2b with other residues is highlighted by the yellow rectangle.