9osg

The partially ruptured LBD state of GluK2/K5 with 5-iodowillardiine and kynurenic acid sodium salt

spinqualitylabelsall models 9osg, resolution 3.83Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9osg is a 4 chain structure with sequence from Aequorea victoria and Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.83Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GRIK5_RAT Receptor for glutamate. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. This receptor binds kainate > quisqualate > glutamate >> AMPA. Publication Abstract from PubMed 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. Structures of partially occupied hetero-tetramers provide insight into kainate receptor activation and desensitization.,Khanra NK, Strauss A, Moreno Wasielewski L, Lenze S, Meyerson J, Reiner A, Levitz J Nat Commun. 2026 Apr 24;17(1):3789. doi: 10.1038/s41467-026-72226-w. PMID:42031800 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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