6x3f

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<StructureSection load='6x3f' size='340' side='right'caption='[[6x3f]], [[Resolution|resolution]] 3.03&Aring;' scene=''>
<StructureSection load='6x3f' size='340' side='right'caption='[[6x3f]], [[Resolution|resolution]] 3.03&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[6x3f]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6X3F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6X3F FirstGlance]. <br>
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<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6X3F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6X3F FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.03&#8491;</td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.03&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CHT:CHOLINE+ION'>CHT</scene></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CHT:CHOLINE+ION'>CHT</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=6x3f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6x3f OCA], [https://pdbe.org/6x3f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6x3f RCSB], [https://www.ebi.ac.uk/pdbsum/6x3f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6x3f ProSAT]</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=6x3f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6x3f OCA], [https://pdbe.org/6x3f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6x3f RCSB], [https://www.ebi.ac.uk/pdbsum/6x3f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6x3f ProSAT]</span></td></tr>
</table>
</table>
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== Disease ==
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<div style="background-color:#fffaf0;">
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[https://www.uniprot.org/uniprot/EAA3_HUMAN EAA3_HUMAN] Hot water reflex epilepsy;Dicarboxylic aminoaciduria. The disease is caused by variants affecting the gene represented in this entry. Disease susceptibility is associated with variants affecting the gene represented in this entry. A deletion at the chromosome 9p24.2 locus, including SLC1A1, has been identified in patients with psychotic disorders (PubMed:21982423). This 84 kb deletion is immediately upstream of the SLC1A1 gene in a regulatory region that contains the full native promoter sequence, extends through exon 1 of the SLC1A1 mRNA, co-segregates with disease in an extended 5-generation pedigree and increases disease risk more than 18-fold for family members (PubMed:23341099).<ref>PMID:21982423</ref> <ref>PMID:23341099</ref>
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== Publication Abstract from PubMed ==
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== Function ==
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Human excitatory amino acid transporter 3 (hEAAT3) mediates glutamate uptake in neurons, intestine, and kidney. Here, we report cryo-EM structures of hEAAT3 in several functional states where the transporter is empty, bound to coupled sodium ions only, or fully loaded with three sodium ions, a proton, and the substrate aspartate. The structures suggest that hEAAT3 operates by an elevator mechanism involving three functionally independent subunits. When the substrate-binding site is near the cytoplasm, it has a remarkably low affinity for the substrate, perhaps facilitating its release and allowing the rapid transport turnover. The mechanism of the coupled uptake of the sodium ions and the substrate is conserved across evolutionarily distant families and is augmented by coupling to protons in EAATs. The structures further suggest a mechanism by which a conserved glutamate residue mediates proton symport.
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[https://www.uniprot.org/uniprot/EAA3_HUMAN EAA3_HUMAN] Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate (PubMed:7914198, PubMed:7521911, PubMed:8857541, PubMed:26690923, PubMed:21123949, PubMed:33658209). Can also transport L-cysteine (PubMed:21123949). Functions as a symporter that transports one amino acid molecule together with two or three Na(+) ions and one proton, in parallel with the counter-transport of one K(+) ion (PubMed:7521911, PubMed:8857541, PubMed:26690923, PubMed:33658209). Mediates Cl(-) flux that is not coupled to amino acid transport; this avoids the accumulation of negative charges due to aspartate and Na(+) symport (PubMed:8857541, PubMed:26690923). Plays an important role in L-glutamate and L-aspartate reabsorption in renal tubuli (PubMed:21123949). Plays a redundant role in the rapid removal of released glutamate from the synaptic cleft, which is essential for terminating the postsynaptic action of glutamate (By similarity). Contributes to glutathione biosynthesis and protection against oxidative stress via its role in L-glutamate and L-cysteine transport (By similarity). Negatively regulated by ARL6IP5 (By similarity).[UniProtKB:P51906][UniProtKB:P51907]<ref>PMID:21123949</ref> <ref>PMID:26690923</ref> <ref>PMID:33658209</ref> <ref>PMID:7521911</ref> <ref>PMID:7914198</ref> <ref>PMID:8857541</ref>
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Cryo-EM structures of excitatory amino acid transporter 3 visualize coupled substrate, sodium, and proton binding and transport.,Qiu B, Matthies D, Fortea E, Yu Z, Boudker O Sci Adv. 2021 Mar 3;7(10). pii: 7/10/eabf5814. doi: 10.1126/sciadv.abf5814. Print, 2021 Mar. PMID:33658209<ref>PMID:33658209</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 6x3f" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Homo sapiens]]
 
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Boudker O]]
[[Category: Boudker O]]
[[Category: Matthies D]]
[[Category: Matthies D]]
[[Category: Qiu B]]
[[Category: Qiu B]]

Current revision

hEAAT3-IFS-Apo

PDB ID 6x3f

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