2.A.22.5.3
Neurotransmitter:sodium symporter of 455 aas, MhsT.  The x-ray structures of two occluded inward-facing states with bound Na⁺ ions and L-tryptophan have been solved (4US4; Malinauskaite et al. 2014).  These structures provide insight into the cytoplasmic release of Na⁺. The switch from outward- to inward-oriented states is centered on the partial unwinding of transmembrane helix 5, facilitated by a conserved GlyX₉Pro motif that opens an intracellular pathway for water to access the Na⁺2 site. Solvation through this TMS 5 pathway may facilitate Na⁺ release from the Na⁺2 site to the inward-open state (Malinauskaite et al. 2014). TMS5 plays a role in the binding and release of Na⁺ from the Na⁺2 site and in mediating conformational changes (Stolzenberg et al. 2017). MhsT of Bacillus halodurans is a transporter of hydrophobic amino acids and a homologue of the eukaryotic SLC6 family of Na⁺ -dependent symporters for amino acids, neurotransmitters, osmolytes, and creatine. A non-helical region in TMS 6 of hydrophobic amino acid transporter MhsT mediates substrate recognition (Focht et al. 2020).