7AWP
Structure of the thermostabilized EAAT1 cryst-II mutant in complex with rubidium and barium ions and the allosteric inhibitor UCPH101
Summary for 7AWP
| Entry DOI | 10.2210/pdb7awp/pdb |
| Descriptor | Excitatory amino acid transporter 1,Neutral amino acid transporter B(0),Excitatory amino acid transporter 1, 2-Amino-5,6,7,8-tetrahydro-4-(4-methoxyphenyl)-7-(naphthalen-1-yl)-5-oxo-4H-chromene-3-carbonitrile, BARIUM ION, ... (4 entities in total) |
| Functional Keywords | excitatory amino acid transporter 1, human glutamate transporter, slc1a3, ion-coupling mechanism, transport protein |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 1 |
| Total formula weight | 57242.92 |
| Authors | Canul-Tec, J.C.,Legrand, P.,Reyes, N. (deposition date: 2020-11-08, release date: 2021-10-13, Last modification date: 2024-01-31) |
| Primary citation | Canul-Tec, J.C.,Kumar, A.,Dhenin, J.,Assal, R.,Legrand, P.,Rey, M.,Chamot-Rooke, J.,Reyes, N. The ion-coupling mechanism of human excitatory amino acid transporters. Embo J., 41:e108341-e108341, 2022 Cited by PubMed Abstract: 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 , are coupled to neurotransmitter binding. Ca competes for a conserved Na site, suggesting a regulatory role for Ca 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. PubMed: 34747040DOI: 10.15252/embj.2021108341 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.91 Å) |
Structure validation
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