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. 2019 Sep 6;6:80. doi: 10.3389/fmolb.2019.00080

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Copyright © 2019 Joseph, Pidathala, Mallela and Penmatsa.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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(A) Topology of neurotransmitter transporters. Discontinuous helices TM1 and TM6 are involved in neurotransmitter recognition. TMs 3, 8, and 10 serve as scaffold helices in the structure. TMs 1–5 and 6–10 display a pseudo-2-fold symmetry. (B) Schematic showing the rocking-bundle type of alternating-access mechanism employed by the NSS members for the transport of substrates. The transport cycle samples multiple conformational states including O_o, O_occ, I_occ, I_o to accomplish transport. (C) Surface electrostatics of dDAT with gating and scaffold helices are represented in different colors (PDB ID: 4XP1). The figure summarizes the discrete regions of the structure that undergo dynamic movements to elicit substrate translocation.