Transport mechanism of the neuronal excitatory amino acid transporter Article Swipe
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· 2020
· Open Access
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· DOI: https://doi.org/10.1101/2020.06.01.127704
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 for 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 conserved glutamate mediates proton symport.
Related Topics
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2020.06.01.127704
- https://www.biorxiv.org/content/biorxiv/early/2020/06/02/2020.06.01.127704.full.pdf
- OA Status
- green
- Cited By
- 3
- References
- 53
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3028766900
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- OpenAlex ID
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https://openalex.org/W3028766900Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2020.06.01.127704Digital Object Identifier
- Title
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Transport mechanism of the neuronal excitatory amino acid transporterWork title
- Type
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preprintOpenAlex work type
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enPrimary language
- Publication year
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2020Year of publication
- Publication date
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2020-06-02Full publication date if available
- Authors
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Biao Qiu, Doreen Matthies, Eva Fortea, Zhiheng Yu, Olga BoudkerList of authors in order
- Landing page
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https://doi.org/10.1101/2020.06.01.127704Publisher landing page
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https://www.biorxiv.org/content/biorxiv/early/2020/06/02/2020.06.01.127704.full.pdfDirect link to full text PDF
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YesWhether a free full text is available
- OA status
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greenOpen access status per OpenAlex
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https://www.biorxiv.org/content/biorxiv/early/2020/06/02/2020.06.01.127704.full.pdfDirect OA link when available
- Concepts
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Symporter, Transporter, Biophysics, Substrate (aquarium), Chemistry, Excitatory postsynaptic potential, Excitatory amino-acid transporter, Glutamate receptor, Amino acid, Glutamate aspartate transporter, Cytoplasm, Biochemistry, Coupling (piping), Sodium, Biology, Materials science, Gene, Receptor, Metallurgy, Ecology, Organic chemistryTop concepts (fields/topics) attached by OpenAlex
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3Total citation count in OpenAlex
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2021: 2, 2020: 1Per-year citation counts (last 5 years)
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53Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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