7npw

<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>

</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>

== Disease ==

[[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.

== Function ==

[[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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== Publication Abstract from PubMed ==

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.

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>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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== References ==

<references/>

[[Category: Kumar, A]]

[[Category: Reyes, N]]

[[Category: Transporter]]