9FRH
CryoEM structure of human rho1 GABAA receptor in complex with (R)-GABOB in the primed state
This is a non-PDB format compatible entry.
Summary for 9FRH
| Entry DOI | 10.2210/pdb9frh/pdb |
| EMDB information | 50714 |
| Descriptor | Gamma-aminobutyric acid receptor subunit rho-1, (R)-amino-3-hydroxybutanoic acid, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total) |
| Functional Keywords | ion channel, translocase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 5 |
| Total formula weight | 286742.63 |
| Authors | Fan, C.,Howard, R.J.,Lindahl, E. (deposition date: 2024-06-18, release date: 2025-07-02, Last modification date: 2025-08-13) |
| Primary citation | 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 Cited by 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: 40750757DOI: 10.1038/s41467-025-61932-6 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.14 Å) |
Structure validation
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