8gnk
From Proteopedia
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== Function == | == Function == | ||
| - | [https://www.uniprot.org/uniprot/SC6A1_RAT SC6A1_RAT] Mediates transport of gamma-aminobutyric acid (GABA) together with sodium and chloride and is responsible for the reuptake of GABA from the synapse (PubMed: | + | [https://www.uniprot.org/uniprot/SC6A1_RAT SC6A1_RAT] Mediates transport of gamma-aminobutyric acid (GABA) together with sodium and chloride and is responsible for the reuptake of GABA from the synapse (PubMed:18054861, PubMed:1975955). The translocation of GABA, however, may also occur in the reverse direction leading to the release of GABA (PubMed:18054861, PubMed:21775701). The direction and magnitude of GABA transport is a consequence of the prevailing thermodynamic conditions, determined by membrane potential and the intracellular and extracellular concentrations of Na(+), Cl(-) and GABA (PubMed:18054861, PubMed:21775701). Also mediates sodium- and chloride-dependent transport of hypotaurine (By similarity).[UniProtKB:P31648]<ref>PMID:18054861</ref> <ref>PMID:1975955</ref> <ref>PMID:21775701</ref> |
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The inhibitory neurotransmitter gamma-aminobutyric acid (GABA) is cleared from the synaptic cleft by the sodium- and chloride-coupled GABA transporter GAT1. Inhibition of GAT1 prolongs the GABAergic signaling at the synapse and is a strategy to treat certain forms of epilepsy. In this study, we present the cryo-electron microscopy structure of Rattus norvegicus GABA transporter 1 (rGAT1) at a resolution of 3.1 A. The structure elucidation was facilitated by epitope transfer of a fragment-antigen binding (Fab) interaction site from the Drosophila dopamine transporter (dDAT) to rGAT1. The structure reveals rGAT1 in a cytosol-facing conformation, with a linear density in the primary binding site that accommodates a molecule of GABA, a displaced ion density proximal to Na site 1 and a bound chloride ion. A unique insertion in TM10 aids the formation of a compact, closed extracellular gate. Besides yielding mechanistic insights into ion and substrate recognition, our study will enable the rational design of specific antiepileptics. | ||
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| + | Cryo-EM structure of GABA transporter 1 reveals substrate recognition and transport mechanism.,Nayak SR, Joseph D, Hofner G, Dakua A, Athreya A, Wanner KT, Kanner BI, Penmatsa A Nat Struct Mol Biol. 2023 Jul;30(7):1023-1032. doi: 10.1038/s41594-023-01011-w. , Epub 2023 Jul 3. PMID:37400654<ref>PMID:37400654</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 8gnk" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
CryoEM structure of cytosol-facing, substrate-bound ratGAT1
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