View source for 8gnk


==CryoEM structure of cytosol-facing, substrate-bound ratGAT1==
<StructureSection load='8gnk' size='340' side='right'caption='[[8gnk]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8gnk]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8GNK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8GNK FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ABU:GAMMA-AMINO-BUTANOIC+ACID'>ABU</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PTY:PHOSPHATIDYLETHANOLAMINE'>PTY</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8gnk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8gnk OCA], [https://pdbe.org/8gnk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8gnk RCSB], [https://www.ebi.ac.uk/pdbsum/8gnk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8gnk ProSAT]</span></td></tr>
</table>
== 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: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> 
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== 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.

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>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 8gnk" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Rattus norvegicus]]
[[Category: Joseph D]]
[[Category: Nayak SR]]
[[Category: Penmatsa A]]