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-Structure paper
タイトル | Cryo-EM structures of excitatory amino acid transporter 3 visualize coupled substrate, sodium, and proton binding and transport. |
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ジャーナル・号・ページ | Sci Adv, Vol. 7, Issue 10, Year 2021 |
掲載日 | 2021年3月3日 |
著者 | Biao Qiu / Doreen Matthies / Eva Fortea / Zhiheng Yu / Olga Boudker / |
PubMed 要旨 | Human excitatory amino acid transporter 3 (hEAAT3) mediates glutamate uptake in neurons, intestine, and kidney. Here, we report cryo-EM structures of hEAAT3 in several functional states where the ...Human excitatory amino acid transporter 3 (hEAAT3) mediates glutamate uptake in neurons, intestine, and kidney. Here, we report cryo-EM structures of hEAAT3 in several functional states where the transporter is empty, bound to coupled sodium ions only, or fully loaded with three sodium ions, a proton, and the substrate aspartate. The structures suggest that hEAAT3 operates by an elevator mechanism involving three functionally independent subunits. When the substrate-binding site is near the cytoplasm, it has a remarkably low affinity for the substrate, perhaps facilitating its release and allowing the rapid transport turnover. The mechanism of the coupled uptake of the sodium ions and the substrate is conserved across evolutionarily distant families and is augmented by coupling to protons in EAATs. The structures further suggest a mechanism by which a conserved glutamate residue mediates proton symport. |
リンク | Sci Adv / PubMed:33658209 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.85 - 3.71 Å |
構造データ | EMDB-22011, PDB-6x2l: EMDB-22014, PDB-6x2z: EMDB-22020, PDB-6x3e: EMDB-22021, PDB-6x3f: EMDB-22022: EMDB-22023: EMDB-22024: |
化合物 | ChemComp-ASP: ChemComp-NA: ChemComp-CHT: |
由来 |
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キーワード | TRANSPORT PROTEIN / humant Excitatory amino acid transporter 3 / hEAAT3 outward-facing / full-bound / Asymmetric / Outward-facing bound / Inward-facing open / hEAAT3 inward-facing Apo state |