The ion‐coupling mechanism of human excitatory amino acid transporters
| hal.structure.identifier | Microbiologie Fondamentale et Pathogénicité [MFP] | |
| dc.contributor.author | CANUL-TEC, Juan | |
| hal.structure.identifier | Microbiologie Fondamentale et Pathogénicité [MFP] | |
| dc.contributor.author | KUMAR, Anand | |
| dc.contributor.author | DHENIN, Jonathan | |
| dc.contributor.author | ASSAL, Redda | |
| hal.structure.identifier | Synchrotron SOLEIL [SSOLEIL] | |
| dc.contributor.author | LEGRAND, Pierre | |
| dc.contributor.author | REY, Martial | |
| hal.structure.identifier | Spectrométrie de Masse pour la Biologie – Mass Spectrometry for Biology [UTechS MSBio] | |
| dc.contributor.author | CHAMOT-ROOKE, Julia | |
| hal.structure.identifier | Microbiologie Fondamentale et Pathogénicité [MFP] | |
| dc.contributor.author | REYES, Nicolas | |
| dc.date.accessioned | 2023-05-15T10:50:32Z | |
| dc.date.available | 2023-05-15T10:50:32Z | |
| dc.date.issued | 2022-01-04 | |
| dc.identifier.issn | 0261-4189 | |
| dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/182127 | |
| dc.description.abstractEn | 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 Ca2+, are coupled to neurotransmitter binding. Ca2+ competes for a conserved Na+ site, suggesting a regulatory role for Ca2+ 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. | |
| dc.description.sponsorship | Centre d'analyse de systèmes complexes dans les environnements complexes - ANR-11-EQPX-0008 | |
| dc.language.iso | en | |
| dc.publisher | EMBO Press | |
| dc.rights | Attribution-NonCommercial 3.0 United States | * |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc/3.0/us/ | * |
| dc.subject.en | cryo-EM | |
| dc.subject.en | neurotransmitter transport | |
| dc.subject.en | permeation and transport | |
| dc.subject.en | solute carrier | |
| dc.subject.en | X-ray crystallography | |
| dc.title.en | The ion‐coupling mechanism of human excitatory amino acid transporters | |
| dc.type | Article de revue | en_US |
| dc.identifier.doi | 10.15252/embj.2021108341 | |
| dc.subject.hal | Sciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire/Biologie structurale [q-bio.BM] | |
| dc.description.sponsorshipEurope | Molecular bases of human excitatory neurotransmitter transport across the plasma membrane | |
| bordeaux.journal | EMBO Journal | en_US |
| bordeaux.page | 377-390 | |
| bordeaux.volume | 41 | |
| bordeaux.hal.laboratories | MFP (Laboratoire Microbiologie Fondamentale et Pathogénicité) - UMR 5234 | en_US |
| bordeaux.issue | 1 | |
| bordeaux.institution | CNRS | |
| bordeaux.peerReviewed | oui | |
| bordeaux.import.source | hal | |
| hal.identifier | pasteur-03795591 | |
| hal.version | 1 | |
| hal.export | false | |
| workflow.import.source | hal | |
| dc.rights.cc | Pas de Licence CC | en_US |
| bordeaux.COinS | ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=EMBO%20Journal&rft.date=2022-01-04&rft.volume=41&rft.issue=1&rft.spage=377-390&rft.epage=377-390&rft.eissn=0261-4189&rft.issn=0261-4189&rft.au=CANUL-TEC,%20Juan&KUMAR,%20Anand&DHENIN,%20Jonathan&ASSAL,%20Redda&LEGRAND,%20Pierre&rft.genre=article |
