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| <StructureSection load='7npw' size='340' side='right'caption='[[7npw]], [[Resolution|resolution]] 3.99Å' scene=''> | | <StructureSection load='7npw' size='340' side='right'caption='[[7npw]], [[Resolution|resolution]] 3.99Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[7npw]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7NPW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NPW FirstGlance]. <br> | | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7NPW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NPW 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=7npw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7npw OCA], [https://pdbe.org/7npw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7npw RCSB], [https://www.ebi.ac.uk/pdbsum/7npw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7npw 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]] 3.99Å</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=7npw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7npw OCA], [https://pdbe.org/7npw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7npw RCSB], [https://www.ebi.ac.uk/pdbsum/7npw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7npw ProSAT]</span></td></tr> |
| </table> | | </table> |
| == 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/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®/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 7npw" style="background-color:#fffaf0;"></div>
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| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Kumar, A]] | | [[Category: Kumar A]] |
| [[Category: Reyes, N]] | | [[Category: Reyes N]] |
| [[Category: Glutamate transporter]]
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| [[Category: Human membrane protein]]
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| [[Category: Membrane protein]]
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| [[Category: Transporter]]
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