9CTS

Best1 + GABA intermediate state 2

9CTS の概要

• エントリーDOI: 10.2210/pdb9cts/pdb
• EMDBエントリー: 45917
• 分子名称: Bestrophin-1, CALCIUM ION, GAMMA-AMINO-BUTANOIC ACID (3 entities in total)
• 機能のキーワード: calcium-activated chloride channel, gaba type a receptor, gaba-bound anion channel, channel-activator complex, membrane protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 338759.23

構造登録者

Owji, A.P.,Kittredge, A.,Zhang, Y.,Yang, T. (登録日: 2024-07-25, 公開日: 2024-09-25)

主引用文献

Wang, J.,Owji, A.P.,Kittredge, A.,Clark, Z.,Zhang, Y.,Yang, T.
GAD65 tunes the functions of Best1 as a GABA receptor and a neurotransmitter conducting channel.
Nat Commun, 15:8051-8051, 2024

PubMed Abstract: Bestrophin-1 (Best1) is an anion channel genetically linked to vision-threatening retinal degenerative channelopathies. Here, we identify interactions between Best1 and both isoforms of glutamic acid decarboxylases (GAD65 and GAD67), elucidate the distinctive influences of GAD65 and GAD67 on Best1's permeability to various anions/neurotransmitters, discover the functionality of Best1 as a γ-Aminobutyric acid (GABA) type A receptor, and solve the structure of GABA-bound Best1. GAD65 and GAD67 both promote Best1-mediated Cl currents, but only GAD65 drastically enhances the permeability of Best1 to glutamate and GABA, for which GAD67 has no effect. GABA binds to Best1 on an extracellular site and stimulates Best1-mediated Cl currents at the nano-molar concentration level. The physiological role of GAD65 as a cell type-specific binding partner and facilitator of Best1 is demonstrated in retinal pigment epithelial cells. Together, our results reveal critical regulators of Best1 and inform a network of membrane transport metabolons formed between bestrophin channels and glutamate metabolic enzymes.

PubMed: 39277606
DOI: 10.1038/s41467-024-52039-5

実験手法

ELECTRON MICROSCOPY (2.45 Å)