9EGM

Human BEST1 bound to GABA in an open state

9EGM の概要

• エントリーDOI: 10.2210/pdb9egm/pdb
• 関連するPDBエントリー: 9EFZ 9EGQ 9EGS 9EGT
• EMDBエントリー: 47991
• 分子名称: Bestrophin-1, CHLORIDE ION, CALCIUM ION, ... (5 entities in total)
• 機能のキーワード: bestrophin, ion channel, gaba, 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: 237975.50

構造登録者

Pant, S.,Long, S.B. (登録日: 2024-11-21, 公開日: 2025-04-09, 最終更新日: 2025-05-14)

主引用文献

Pant, S.,Tam, S.W.,Long, S.B.
The pentameric chloride channel BEST1 is activated by extracellular GABA.
Proc.Natl.Acad.Sci.USA, 122:e2424474122-e2424474122, 2025

PubMed Abstract: Bestrophin-1 (BEST1) is a chloride channel expressed in the eye and other tissues of the body. A link between BEST1 and the principal inhibitory neurotransmitter -aminobutyric acid (GABA) has been proposed. The most appreciated receptors for extracellular GABA are the GABA G-protein-coupled receptors and the pentameric GABA chloride channels, both of which have fundamental roles in the central nervous system. Here, we demonstrate that BEST1 is directly activated by GABA. Through functional studies and atomic-resolution structures of human and chicken BEST1, we identify a GABA binding site on the channel's extracellular side and determine the mechanism by which GABA binding stabilizes opening of the channel's central gate. This same gate, "the neck," is activated by intracellular [Ca], indicating that BEST1 is controlled by ligands from both sides of the membrane. The studies demonstrate that BEST1, which shares no structural homology with GABA receptors, is a GABA-activated chloride channel. The physiological implications of this finding remain to be studied.

PubMed: 40249777
DOI: 10.1073/pnas.2424474122

実験手法

ELECTRON MICROSCOPY (2.45 Å)