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PDBsum entry 4us4
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Transport protein
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PDB id
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4us4
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References listed in PDB file
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Key reference
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Title
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A mechanism for intracellular release of na+ by neurotransmitter/sodium symporters.
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Authors
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L.Malinauskaite,
M.Quick,
L.Reinhard,
J.A.Lyons,
H.Yano,
J.A.Javitch,
P.Nissen.
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Ref.
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Nat Struct Biol, 2014,
21,
1006-1012.
[DOI no: ]
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PubMed id
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Note: In the PDB file this reference is
annotated as "TO BE PUBLISHED". The citation details given above have
been manually determined.
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Abstract
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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.
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