9PKZ
Alpha1/Beta Heteromeric Glycine receptor in the presence of 0.200 mM strychnine and 0.02 mM ivermectin
Summary for 9PKZ
| Entry DOI | 10.2210/pdb9pkz/pdb |
| EMDB information | 71708 |
| Descriptor | Glycine receptor, alpha 1, Glycine receptor beta subunit 2, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total) |
| Functional Keywords | ion channel, pentameric, glycine, receptor, transport protein |
| Biological source | Danio rerio (zebrafish) More |
| Total number of polymer chains | 5 |
| Total formula weight | 283124.24 |
| Authors | Gibbs, E.,Chakrapani, S. (deposition date: 2025-07-14, release date: 2026-01-07, Last modification date: 2026-07-22) |
| Primary citation | Gibbs, E.,Feddersen, B.,Kindig, K.J.,Seiferth, D.,Biggin, P.C.,Chakrapani, S. Structural basis for domain coupling in heteromeric glycine receptors revealed by an atypical allosteric agonist. Sci Adv, 12:eaeb2036-eaeb2036, 2026 Cited by PubMed Abstract: Glycine receptors (GlyRs), pentameric ligand-gated ion channels (pLGICs), mediate sensory and motor functions. GlyR functional states are well characterized; however, structural details of transitions between states remain undefined. Here, we determined cryo-electron microscopy structures of GlyRα1β (with gephyrin E-domain) at varying concentrations of ivermectin, a transmembrane domain (TMD) allosteric agonist, and at saturating concentrations of strychnine, a competitive antagonist at the extracellular domain (ECD). Electrophysiology shows that ivermectin activates GlyR even with strychnine present. Structures with both ligands reveal intermediate states featuring a desensitized TMD and an ECD between closed and desensitized conformations, providing insights into domain cooperativity and ligand efficacy. Molecular dynamics simulations show how ivermectin affects strychnine dynamics. These data support a model where ivermectin activates GlyRs through a concerted and near-symmetric TMD mechanism, whereas allosteric ECD motions are graded and spatially heterogeneous. These findings reveal unanticipated features of GlyR gating and establish principles of allosteric modulation applicable to pLGICs. PubMed: 41686897DOI: 10.1126/sciadv.aeb2036 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.89 Å) |
Structure validation
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