8GNK
CryoEM structure of cytosol-facing, substrate-bound ratGAT1
Summary for 8GNK
| Entry DOI | 10.2210/pdb8gnk/pdb |
| EMDB information | 34167 |
| Descriptor | Sodium- and chloride-dependent GABA transporter 1, Fragment antigen binding light chain, fragment antigen binding 9D5 heavy chain, ... (10 entities in total) |
| Functional Keywords | neurotransmitter sodium symporter, gaba transporter, solute carrier 6, secondary active transport, membrane protein |
| Biological source | Rattus norvegicus (Norway rat) More |
| Total number of polymer chains | 3 |
| Total formula weight | 113784.63 |
| Authors | Nayak, S.R.,Joseph, D.,Penmatsa, A. (deposition date: 2022-08-24, release date: 2023-05-31, Last modification date: 2024-10-23) |
| Primary citation | Nayak, S.R.,Joseph, D.,Hofner, G.,Dakua, A.,Athreya, A.,Wanner, K.T.,Kanner, B.I.,Penmatsa, A. Cryo-EM structure of GABA transporter 1 reveals substrate recognition and transport mechanism. Nat.Struct.Mol.Biol., 30:1023-1032, 2023 Cited by PubMed Abstract: 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 Å. 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. PubMed: 37400654DOI: 10.1038/s41594-023-01011-w PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.1 Å) |
Structure validation
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