7npw: Difference between revisions

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==Cryo-EM structure of Human excitatory amino acid transporters-1 (EAAT1) in potassium buffer==

== Structural highlights ==

<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>

<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>

</table>

== 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.

== 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®/PubMed®, a database of the U.S. National Library of Medicine.<br>

</div>

== References ==

__TOC__

</StructureSection>

[[Category: Large Structures]]

[[Category: Kumar A]]

[[Category: Kumar, A]]

[[Category: Reyes N]]

[[Category: Reyes, N]]

[[Category: Glutamate transporter]]

[[Category: Human membrane protein]]

[[Category: Membrane protein]]

[[Category: Transporter]]

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@@ Line 1: / Line 1: @@
 ==Cryo-EM structure of Human excitatory amino acid transporters-1 (EAAT1) in potassium buffer==
-<StructureSection load='7npw' size='340' side='right'caption='[[7npw]]' scene=''>
+<StructureSection load='7npw' size='340' side='right'caption='[[7npw]], [[Resolution|resolution]] 3.99&Aring;' scene=''>
 == Structural highlights ==
-<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>
+<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>
 </table>
+== 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.
+<div style="background-color:#fffaf0;">
+== 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>
+</div>
+<div class="pdbe-citations 7npw" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
 __TOC__
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Kumar A]]
+[[Category: Kumar, A]]
-[[Category: Reyes N]]
+[[Category: Reyes, N]]
+[[Category: Glutamate transporter]]
+[[Category: Human membrane protein]]
+[[Category: Membrane protein]]
+[[Category: Transporter]]