9FRF

CryoEM structure of human rho1 GABAA receptor in complex with (R)-GABOB in the desensitized state

これはPDB形式変換不可エントリーです。

9FRF の概要

• エントリーDOI: 10.2210/pdb9frf/pdb
• EMDBエントリー: 50713
• 分子名称: Gamma-aminobutyric acid receptor subunit rho-1, (R)-amino-3-hydroxybutanoic acid, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• 機能のキーワード: ion channel, translocase
• 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: 285345.18

構造登録者

Fan, C.,Howard, R.J.,Lindahl, E. (登録日: 2024-06-18, 公開日: 2025-07-02, 最終更新日: 2025-08-13)

主引用文献

Fan, C.,Cowgill, J.,Howard, R.J.,Lindahl, E.
Cryo-EM structures of rho 1 GABA A receptors with antagonist and agonist drugs.
Nat Commun, 16:7077-7077, 2025

PubMed Abstract: The family of ρ-type GABA receptors includes potential therapeutic targets in several neurological conditions, and features distinctive pharmacology compared to other subtypes. Here we report four cryo-EM structures with previously unresolved ligands, electrophysiology recordings, and molecular dynamics simulations to characterize binding and conformational impact of the drugs THIP (a non-opioid analgesic), CGP36742 (a phosphinic acid) and GABOB (an anticonvulsant) on a human ρ1 GABA receptor. A distinctive binding pose of THIP in ρ1 versus α4β3δ GABA receptors offers a rationale for its inverse effects on these subtypes. CGP36742 binding is similar to the canonical ρ-type inhibitor TPMPA, supporting a shared mechanism of action among phosphinic acids. Binding of GABOB is similar to GABA, but produces a mixture of partially-locked and desensitized states, likely underlying weaker agonist activity. Together, these results elucidate interactions of a ρ-type GABA receptor with therapeutic drugs, offering mechanistic insights and a basis for further pharmaceutical development.

PubMed: 40750757
DOI: 10.1038/s41467-025-61932-6

実験手法

ELECTRON MICROSCOPY (2.41 Å)