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hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorCANUL-TEC, Juan
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorKUMAR, Anand
dc.contributor.authorDHENIN, Jonathan
dc.contributor.authorASSAL, Redda
hal.structure.identifierSynchrotron SOLEIL [SSOLEIL]
dc.contributor.authorLEGRAND, Pierre
dc.contributor.authorREY, Martial
hal.structure.identifierSpectrométrie de Masse pour la Biologie – Mass Spectrometry for Biology [UTechS MSBio]
dc.contributor.authorCHAMOT-ROOKE, Julia
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorREYES, Nicolas
dc.date.accessioned2023-05-15T10:50:32Z
dc.date.available2023-05-15T10:50:32Z
dc.date.issued2022-01-04
dc.identifier.issn0261-4189
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/182127
dc.description.abstractEnExcitatory 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.sponsorshipCentre d'analyse de systèmes complexes dans les environnements complexes
dc.language.isoen
dc.publisherEMBO Press
dc.rightsAttribution-NonCommercial 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc/3.0/us/*
dc.subject.encryo-EM
dc.subject.enneurotransmitter transport
dc.subject.enpermeation and transport
dc.subject.ensolute carrier
dc.subject.enX-ray crystallography
dc.title.enThe ion‐coupling mechanism of human excitatory amino acid transporters
dc.typeArticle de revueen_US
dc.identifier.doi10.15252/embj.2021108341
dc.subject.halSciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire/Biologie structurale [q-bio.BM]
dc.description.sponsorshipEuropeMolecular bases of human excitatory neurotransmitter transport across the plasma membrane
bordeaux.journalEMBO Journalen_US
bordeaux.page377-390
bordeaux.volume41
bordeaux.hal.laboratoriesMFP (Laboratoire Microbiologie Fondamentale et Pathogénicité) - UMR 5234en_US
bordeaux.issue1
bordeaux.institutionCNRS
bordeaux.peerReviewedoui
bordeaux.import.sourcehal
hal.identifierpasteur-03795591
hal.version1
hal.exportfalse
workflow.import.sourcehal
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_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


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