9OSI
The intact LBD state of GluK2/K5 with alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)
Summary for 9OSI
| Entry DOI | 10.2210/pdb9osi/pdb |
| EMDB information | 70807 |
| Descriptor | Glutamate receptor ionotropic, kainate 5,Green fluorescent protein chimera, Glutamate receptor ionotropic, kainate 2 (2 entities in total) |
| Functional Keywords | kainate receptor, ionotropic glutamate receptor, membrane protein, ligand-gated ion channel, signaling protein |
| Biological source | Rattus norvegicus (Norway rat) More |
| Total number of polymer chains | 4 |
| Total formula weight | 459316.86 |
| Authors | |
| Primary citation | Khanra, N.K.,Strauss, A.,Moreno Wasielewski, L.,Lenze, S.,Meyerson, J.,Reiner, A.,Levitz, J. Structures of partially occupied hetero-tetramers provide insight into kainate receptor activation and desensitization. Nat Commun, 17:-, 2026 Cited by PubMed Abstract: Kainate receptors (KARs) are critical mediators and modulators of synaptic transmission which undergo rapid activation and desensitization upon binding of the neurotransmitter glutamate. Under various physiological and pharmacological conditions agonist binding likely occurs to only a subset of subunits within these tetrameric receptors, motivating an analysis of the functional and conformational effects of partial versus complete ligand occupancy. Here we report cryo-EM structures of the GluK2/GluK5 hetero-tetramer under partially-occupied conditions using 5-iodowillardiine and AMPA as GluK5-selective agonists. High-resolution pre-active state structures containing closed/open ligand binding domain (LBD) dimers with intact interfaces reveal gating-associated interface reshaping, inter-dimer motions, and pore-linker repositioning in response to asymmetric agonist binding. Interfacial LBD mutations to a central cluster formed by the GluK5 subunits and to an inter-dimer interface between GluK2 and GluK5 subunits, highlight the roles of interactions between LBD dimers in controlling receptor function, including the distinct slow deactivation of GluK5-containing receptors. Finally, the absence or presence of intact, partially, and fully ruptured LBD interfaces under different ligand conditions allows us to propose a revised model of stepwise ionotropic glutamate receptor activation and desensitization. PubMed: 42031800DOI: 10.1038/s41467-026-72226-w PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.95 Å) |
Structure validation
No wwPDB Validation report is currently available for this entry.
