@article {8466,
	title = {Cryo-EM structure of GABA transporter 1 reveals substrate recognition and transport mechanism [National Cryo-Electron Microscopy Facility]},
	journal = {Nat Struct Mol Biol},
	year = {2023},
	month = {2023 Jul 03},
	abstract = {<p>The inhibitory neurotransmitter γ-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 {\r 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.</p>
},
	issn = {1545-9985},
	doi = {10.1038/s41594-023-01011-w},
	url = {https://www.nature.com/articles/s41594-023-01011-w},
	author = {Nayak, Smruti Ranjan and Joseph, Deepthi and H{\"o}fner, Georg and Dakua, Archishman and Athreya, Arunabh and Wanner, Klaus T and Kanner, Baruch I and Penmatsa, Aravind}
}
