8GNK

CryoEM structure of cytosol-facing, substrate-bound ratGAT1

8GNK の概要

• エントリーDOI: 10.2210/pdb8gnk/pdb
• EMDBエントリー: 34167
• 分子名称: Sodium- and chloride-dependent GABA transporter 1, Fragment antigen binding light chain, fragment antigen binding 9D5 heavy chain, ... (10 entities in total)
• 機能のキーワード: neurotransmitter sodium symporter, gaba transporter, solute carrier 6, secondary active transport, membrane protein
• 由来する生物種: Rattus norvegicus (Norway rat); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 113784.63

構造登録者

Nayak, S.R.,Joseph, D.,Penmatsa, A. (登録日: 2022-08-24, 公開日: 2023-05-31, 最終更新日: 2024-10-23)

主引用文献

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

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: 37400654
DOI: 10.1038/s41594-023-01011-w

実験手法

ELECTRON MICROSCOPY (3.1 Å)