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-Structure paper
Title | Symport and antiport mechanisms of human glutamate transporters. |
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Journal, issue, pages | Nat Commun, Vol. 14, Issue 1, Page 2579, Year 2023 |
Publish date | May 4, 2023 |
Authors | Biao Qiu / Olga Boudker / |
PubMed 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 ...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. |
External links | Nat Commun / PubMed:37142617 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.44 - 3.42 Å |
Structure data | EMDB-26985, PDB-8ctc: EMDB-26986, PDB-8ctd: EMDB-26997, PDB-8cua: EMDB-26998, PDB-8cud: EMDB-27000, PDB-8cui: EMDB-27001, PDB-8cuj: EMDB-27006, PDB-8cv2: EMDB-27007, PDB-8cv3: |
Chemicals | ChemComp-GLU: ChemComp-NA: ChemComp-HG: ChemComp-HOH: ChemComp-K: |
Source |
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Keywords | TRANSPORT PROTEIN |