4us3

Publication Abstract from PubMed

Neurotransmitter/sodium symporters (NSSs) terminate synaptic signal transmission by Na+-dependent reuptake of released neurotransmitters. Key conformational states have been reported for the bacterial homolog LeuT and an inhibitor-bound Drosophila dopamine transporter. However, a coherent mechanism of Na+-driven transport has not been described. Here, we present two crystal structures of MhsT, an NSS member from Bacillus halodurans, in occluded inward-facing states with bound Na+ ions and L-tryptophan, providing 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 Na2 site. We propose a mechanism, based on our structural and functional findings, in which solvation through the TM5 pathway facilitates Na+ release from Na2 and the transition to an inward-open state.

A mechanism for intracellular release of Na by neurotransmitter/sodium symporters.,Malinauskaite L, Quick M, Reinhard L, Lyons JA, Yano H, Javitch JA, Nissen P Nat Struct Mol Biol. 2014 Oct 5. doi: 10.1038/nsmb.2894. PMID:25282149^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.