Symport and antiport mechanisms of human glutamate transporters.
| Publication Type | Academic Article |
| Authors | Qiu B, Boudker O |
| Journal | Nat Commun |
| Volume | 14 |
| Issue | 1 |
| Pagination | 2579 |
| Date Published | 05/04/2023 |
| ISSN | 2041-1723 |
| Keywords | Amino Acid Transport System X-AG, Glutamic Acid |
| Abstract | Excitatory amino acid transporters (EAATs) uptake glutamate into glial cells and neurons. EAATs achieve million-fold transmitter gradients by symporting it with three sodium ions and a proton, and countertransporting a potassium ion via an elevator mechanism. Despite the availability of structures, the symport and antiport mechanisms still need to be clarified. We report high-resolution cryo-EM structures of human EAAT3 bound to the neurotransmitter glutamate with symported ions, potassium ions, sodium ions alone, or without ligands. We show that an evolutionarily conserved occluded translocation intermediate has a dramatically higher affinity for the neurotransmitter and the countertransported potassium ion than outward- or inward-facing transporters and plays a crucial role in ion coupling. We propose a comprehensive ion coupling mechanism involving a choreographed interplay between bound solutes, conformations of conserved amino acid motifs, and movements of the gating hairpin and the substrate-binding domain. |
| DOI | 10.1038/s41467-023-38120-5 |
| PubMed ID | 37142617 |
| PubMed Central ID | PMC10160106 |