7awl

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==Structure of the thermostabilized EAAT1 cryst-II mutant in complex with barium and the allosteric inhibitor UCPH101==
==Structure of the thermostabilized EAAT1 cryst-II mutant in complex with barium and the allosteric inhibitor UCPH101==
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<StructureSection load='7awl' size='340' side='right'caption='[[7awl]]' scene=''>
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<StructureSection load='7awl' size='340' side='right'caption='[[7awl]], [[Resolution|resolution]] 3.70&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AWL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AWL FirstGlance]. <br>
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<table><tr><td colspan='2'>[[7awl]] is a 1 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=7AWL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AWL FirstGlance]. <br>
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</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=7awl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7awl OCA], [https://pdbe.org/7awl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7awl RCSB], [https://www.ebi.ac.uk/pdbsum/7awl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7awl ProSAT]</span></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.7&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6Z6:2-AMINO-5,6,7,8-TETRAHYDRO-4-(4-METHOXYPHENYL)-7-(NAPHTHALEN-1-YL)-5-OXO-4H-CHROMENE-3-CARBONITRILE'>6Z6</scene>, <scene name='pdbligand=BA:BARIUM+ION'>BA</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7awl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7awl OCA], [https://pdbe.org/7awl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7awl RCSB], [https://www.ebi.ac.uk/pdbsum/7awl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7awl ProSAT]</span></td></tr>
</table>
</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/EAA1_HUMAN EAA1_HUMAN] Alternating hemiplegia of childhood;Episodic ataxia type 6. The disease is caused by mutations affecting the gene represented in this entry.
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== Function ==
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[https://www.uniprot.org/uniprot/AAAT_HUMAN AAAT_HUMAN] Sodium-dependent amino acids transporter that has a broad substrate specificity, with a preference for zwitterionic amino acids. It accepts as substrates all neutral amino acids, including glutamine, asparagine, and branched-chain and aromatic amino acids, and excludes methylated, anionic, and cationic amino acids (PubMed:8702519). Through binding of the fusogenic protein syncytin-1/ERVW-1 may mediate trophoblasts syncytialization, the spontaneous fusion of their plasma membranes, an essential process in placental development (PubMed:10708449, PubMed:23492904).<ref>PMID:10708449</ref> <ref>PMID:23492904</ref> <ref>PMID:8702519</ref> (Microbial infection) Acts as a cell surface receptor for Feline endogenous virus RD114.<ref>PMID:10051606</ref> <ref>PMID:10196349</ref> (Microbial infection) Acts as a cell surface receptor for Baboon M7 endogenous virus.<ref>PMID:10196349</ref> (Microbial infection) Acts as a cell surface receptor for type D simian retroviruses.<ref>PMID:10196349</ref> [https://www.uniprot.org/uniprot/EAA1_HUMAN EAA1_HUMAN] Transports L-glutamate and also L- and D-aspartate. Essential for terminating the postsynaptic action of glutamate by rapidly removing released glutamate from the synaptic cleft. Acts as a symport by cotransporting sodium.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Excitatory amino acid transporters (EAATs) maintain glutamate gradients in the brain essential for neurotransmission and to prevent neuronal death. They use ionic gradients as energy source and co-transport transmitter into the cytoplasm with Na(+) and H(+) , while counter-transporting K(+) to re-initiate the transport cycle. However, the molecular mechanisms underlying ion-coupled transport remain incompletely understood. Here, we present 3D X-ray crystallographic and cryo-EM structures, as well as thermodynamic analysis of human EAAT1 in different ion bound conformations, including elusive counter-transport ion bound states. Binding energies of Na(+) and H(+) , and unexpectedly Ca(2+) , are coupled to neurotransmitter binding. Ca(2+) competes for a conserved Na(+) site, suggesting a regulatory role for Ca(2+) in glutamate transport at the synapse, while H(+) binds to a conserved glutamate residue stabilizing substrate occlusion. The counter-transported ion binding site overlaps with that of glutamate, revealing the K(+) -based mechanism to exclude the transmitter during the transport cycle and to prevent its neurotoxic release on the extracellular side.
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The ion-coupling mechanism of human excitatory amino acid transporters.,Canul-Tec JC, Kumar A, Dhenin J, Assal R, Legrand P, Rey M, Chamot-Rooke J, Reyes N EMBO J. 2021 Nov 8:e108341. doi: 10.15252/embj.2021108341. PMID:34747040<ref>PMID:34747040</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 7awl" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Canul-Tec JC]]
[[Category: Canul-Tec JC]]
[[Category: Legrand P]]
[[Category: Legrand P]]
[[Category: Reyes N]]
[[Category: Reyes N]]

Current revision

Structure of the thermostabilized EAAT1 cryst-II mutant in complex with barium and the allosteric inhibitor UCPH101

PDB ID 7awl

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