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| ==Crystal structure of T355V, S354A, K288A LeuT mutant in complex with alanine and sodium== | | ==Crystal structure of T355V, S354A, K288A LeuT mutant in complex with alanine and sodium== |
| <StructureSection load='3tu0' size='340' side='right' caption='[[3tu0]], [[Resolution|resolution]] 2.99Å' scene=''> | | <StructureSection load='3tu0' size='340' side='right'caption='[[3tu0]], [[Resolution|resolution]] 2.99Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[3tu0]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"aquifex_aeolicus"_huber_and_stetter_2001 "aquifex aeolicus" huber and stetter 2001]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TU0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TU0 FirstGlance]. <br> | | <table><tr><td colspan='2'>[[3tu0]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Aquifex_aeolicus Aquifex aeolicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TU0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TU0 FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ALA:ALANINE'>ALA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.994Å</td></tr> |
| <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2a65|2a65]], [[3tt1|3tt1]], [[3tt3|3tt3]]</td></tr> | | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ALA:ALANINE'>ALA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> |
| <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">snf, aq_2077 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=63363 "Aquifex aeolicus" Huber and Stetter 2001])</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=3tu0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tu0 OCA], [https://pdbe.org/3tu0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tu0 RCSB], [https://www.ebi.ac.uk/pdbsum/3tu0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tu0 ProSAT]</span></td></tr> |
| <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3tu0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tu0 OCA], [http://pdbe.org/3tu0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3tu0 RCSB], [http://www.ebi.ac.uk/pdbsum/3tu0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3tu0 ProSAT]</span></td></tr> | |
| </table> | | </table> |
| <div style="background-color:#fffaf0;">
| | == Function == |
| == Publication Abstract from PubMed == | | [https://www.uniprot.org/uniprot/O67854_AQUAE O67854_AQUAE] |
| Neurotransmitter sodium symporters are integral membrane proteins that remove chemical transmitters from the synapse and terminate neurotransmission mediated by serotonin, dopamine, noradrenaline, glycine and GABA (gamma-aminobutyric acid). Crystal structures of the bacterial homologue, LeuT, in substrate-bound outward-occluded and competitive inhibitor-bound outward-facing states have advanced our mechanistic understanding of neurotransmitter sodium symporters but have left fundamental questions unanswered. Here we report crystal structures of LeuT mutants in complexes with conformation-specific antibody fragments in the outward-open and inward-open states. In the absence of substrate but in the presence of sodium the transporter is outward-open, illustrating how the binding of substrate closes the extracellular gate through local conformational changes: hinge-bending movements of the extracellular halves of transmembrane domains 1, 2 and 6, together with translation of extracellular loop 4. The inward-open conformation, by contrast, involves large-scale conformational changes, including a reorientation of transmembrane domains 1, 2, 5, 6 and 7, a marked hinge bending of transmembrane domain 1a and occlusion of the extracellular vestibule by extracellular loop 4. These changes close the extracellular gate, open an intracellular vestibule, and largely disrupt the two sodium sites, thus providing a mechanism by which ions and substrate are released to the cytoplasm. The new structures establish a structural framework for the mechanism of neurotransmitter sodium symporters and their modulation by therapeutic and illicit substances.
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| X-ray structures of LeuT in substrate-free outward-open and apo inward-open states.,Krishnamurthy H, Gouaux E Nature. 2012 Jan 9. doi: 10.1038/nature10737. PMID:22230955<ref>PMID:22230955</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 3tu0" style="background-color:#fffaf0;"></div>
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| ==See Also== | | ==See Also== |
| *[[Leucine transporter|Leucine transporter]] | | *[[Leucine transporter|Leucine transporter]] |
| == References ==
| | *[[Symporter 3D structures|Symporter 3D structures]] |
| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Aquifex aeolicus huber and stetter 2001]] | | [[Category: Aquifex aeolicus]] |
| [[Category: Gouaux, E]] | | [[Category: Large Structures]] |
| [[Category: Krishnamurthy, H]] | | [[Category: Gouaux E]] |
| [[Category: Leut-fold]] | | [[Category: Krishnamurthy H]] |
| [[Category: Plasma membrane]]
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| [[Category: Sodium-dependent amino acid transporter]]
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| [[Category: Transport protein]]
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