View source for 6xwm


==Mechanism of substrate release in neurotransmitter:sodium symporters: the structure of LeuT in an inward-facing occluded conformation==
<StructureSection load='6xwm' size='340' side='right'caption='[[6xwm]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6xwm]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Aquifex_aeolicus_VF5 Aquifex aeolicus VF5]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XWM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XWM FirstGlance]. <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 id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PHE:PHENYLALANINE'>PHE</scene></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=6xwm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xwm OCA], [https://pdbe.org/6xwm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xwm RCSB], [https://www.ebi.ac.uk/pdbsum/6xwm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xwm ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/O67854_AQUAE O67854_AQUAE] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Neurotransmitter:sodium symporters (NSS) are conserved from bacteria to man and serve as targets for drugs, including antidepressants and psychostimulants. Here we report the X-ray structure of the prokaryotic NSS member, LeuT, in a Na(+)/substrate-bound, inward-facing occluded conformation. To obtain this structure, we were guided by findings from single-molecule fluorescence spectroscopy and molecular dynamics simulations indicating that L-Phe binding and mutation of the conserved N-terminal Trp8 to Ala both promote an inward-facing state. Compared to the outward-facing occluded conformation, our structure reveals a major tilting of the cytoplasmic end of transmembrane segment (TM) 5, which, together with release of the N-terminus but without coupled movement of TM1, opens a wide cavity towards the second Na(+) binding site. The structure of this key intermediate in the LeuT transport cycle, in the context of other NSS structures, leads to the proposal of an intracellular release mechanism of substrate and ions in NSS proteins.

X-ray structure of LeuT in an inward-facing occluded conformation reveals mechanism of substrate release.,Gotfryd K, Boesen T, Mortensen JS, Khelashvili G, Quick M, Terry DS, Missel JW, LeVine MV, Gourdon P, Blanchard SC, Javitch JA, Weinstein H, Loland CJ, Nissen P, Gether U Nat Commun. 2020 Feb 21;11(1):1005. doi: 10.1038/s41467-020-14735-w. PMID:32081981<ref>PMID:32081981</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6xwm" style="background-color:#fffaf0;"></div>

==See Also==
*[[Leucine transporter|Leucine transporter]]
*[[Symporter 3D structures|Symporter 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Aquifex aeolicus VF5]]
[[Category: Large Structures]]
[[Category: Boesen T]]
[[Category: Gether U]]
[[Category: Gotfryd K]]
[[Category: Loland CJ]]
[[Category: Nissen P]]