7xr4: Difference between revisions
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==Structure of human excitatory amino acid transporter 2 (EAAT2) in complex with glutamate== | ==Structure of human excitatory amino acid transporter 2 (EAAT2) in complex with glutamate== | ||
<StructureSection load='7xr4' size='340' side='right'caption='[[7xr4]]' scene=''> | <StructureSection load='7xr4' size='340' side='right'caption='[[7xr4]], [[Resolution|resolution]] 3.40Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7XR4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7XR4 FirstGlance]. <br> | <table><tr><td colspan='2'>[[7xr4]] 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=7XR4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7XR4 FirstGlance]. <br> | ||
</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=7xr4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7xr4 OCA], [https://pdbe.org/7xr4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7xr4 RCSB], [https://www.ebi.ac.uk/pdbsum/7xr4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7xr4 ProSAT]</span></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]] 3.4Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=PC1:1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE'>PC1</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</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=7xr4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7xr4 OCA], [https://pdbe.org/7xr4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7xr4 RCSB], [https://www.ebi.ac.uk/pdbsum/7xr4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7xr4 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Disease == | |||
[https://www.uniprot.org/uniprot/EAA2_HUMAN EAA2_HUMAN] Non-specific early-onset epileptic encephalopathy. The disease is caused by variants affecting the gene represented in this entry. | |||
== Function == | |||
[https://www.uniprot.org/uniprot/EAA2_HUMAN EAA2_HUMAN] Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate (PubMed:14506254, PubMed:15265858, PubMed:26690923, PubMed:7521911). 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:14506254). 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:14506254). Essential for the rapid removal of released glutamate from the synaptic cleft, and for terminating the postsynaptic action of glutamate (By similarity).[UniProtKB:P43006]<ref>PMID:15265858</ref> <ref>PMID:26690923</ref> <ref>PMID:7521911</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
In the central nervous system (CNS), excitatory amino acid transporters (EAATs) mediate the uptake of excitatory neurotransmitter glutamate and maintain its low concentrations in the synaptic cleft for avoiding neuronal cytotoxicity. Dysfunction of EAATs can lead to many psychiatric diseases. Here we report cryo-EM structures of human EAAT2 in an inward-facing conformation, in the presence of substrate glutamate or selective inhibitor WAY-213613. The glutamate is coordinated by extensive hydrogen bonds and further stabilized by HP2. The inhibitor WAY-213613 occupies a similar binding pocket to that of the substrate glutamate. Upon association with the WAY-213613, the HP2 undergoes a substantial conformational change, and in turn stabilizes the inhibitor binding by forming hydrophobic interactions. Electrophysiological experiments elucidate that the unique S441 plays pivotal roles in the binding of hEAAT2 with glutamate or WAY-213613, and the I464-L467-V468 cluster acts as a key structural determinant for the selective inhibition of this transporter by WAY-213613. | |||
Structural basis of ligand binding modes of human EAAT2.,Zhang Z, Chen H, Geng Z, Yu Z, Li H, Dong Y, Zhang H, Huang Z, Jiang J, Zhao Y Nat Commun. 2022 Jun 9;13(1):3329. doi: 10.1038/s41467-022-31031-x. PMID:35680945<ref>PMID:35680945</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7xr4" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Zhang Z]] | [[Category: Zhang Z]] | ||
[[Category: Zhao Y]] | [[Category: Zhao Y]] | ||