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==Crystal Structure of the Bacterial NSS Member MhsT in an Occluded Inward-Facing State (lipidic cubic phase form)==
==Crystal Structure of the Bacterial NSS Member MhsT in an Occluded Inward-Facing State (lipidic cubic phase form)==
<StructureSection load='4us4' size='340' side='right' caption='[[4us4]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
<StructureSection load='4us4' size='340' side='right'caption='[[4us4]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4us4]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4US4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4US4 FirstGlance]. <br>
<table><tr><td colspan='2'>[[4us4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Alkalihalobacillus_halodurans_C-125 Alkalihalobacillus halodurans C-125]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4US4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4US4 FirstGlance]. <br>
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=78M:(2S)-2,3-DIHYDROXYPROPYL(7Z)-PENTADEC-7-ENOATE'>78M</scene>, <scene name='pdbligand=78N:(2R)-2,3-DIHYDROXYPROPYL(7Z)-PENTADEC-7-ENOATE'>78N</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=TRP:TRYPTOPHAN'>TRP</scene><br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4us3|4us3]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=78M:(2S)-2,3-DIHYDROXYPROPYL(7Z)-PENTADEC-7-ENOATE'>78M</scene>, <scene name='pdbligand=78N:(2R)-2,3-DIHYDROXYPROPYL(7Z)-PENTADEC-7-ENOATE'>78N</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=TRP:TRYPTOPHAN'>TRP</scene></td></tr>
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4us4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4us4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4us4 RCSB], [http://www.ebi.ac.uk/pdbsum/4us4 PDBsum]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4us4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4us4 OCA], [https://pdbe.org/4us4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4us4 RCSB], [https://www.ebi.ac.uk/pdbsum/4us4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4us4 ProSAT]</span></td></tr>
<table>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q9KDT3_HALH5 Q9KDT3_HALH5]
<div style="background-color:#fffaf0;">
== 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<ref>PMID:25282149</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4us4" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Javitch, J A.]]
[[Category: Alkalihalobacillus halodurans C-125]]
[[Category: Lyons, J A.]]
[[Category: Large Structures]]
[[Category: Malinauskaite, L.]]
[[Category: Javitch JA]]
[[Category: Nissen, P.]]
[[Category: Lyons JA]]
[[Category: Quick, M.]]
[[Category: Malinauskaite L]]
[[Category: Reinhard, L.]]
[[Category: Nissen P]]
[[Category: Yano, H.]]
[[Category: Quick M]]
[[Category: Amino acid transporter]]
[[Category: Reinhard L]]
[[Category: Leut fold]]
[[Category: Yano H]]
[[Category: Membrane protein]]
[[Category: Neurotransmitter]]
[[Category: Neurotransmitter sodium symporter family]]
[[Category: Secondary transporter]]
[[Category: Transport protein]]
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