9n4r

Composite map for GluK2-0xNeto2 in the open state, in complex with the positive allosteric modulator BPAM344 and agonist kainate

spinqualitylabelsall models 9n4r, resolution 3.48Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9n4r is a 4 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.48Å Ligands: 2J9, BMA, KAI, MAN, NAG, POV Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GRIK2_RAT Ionotropic glutamate receptor. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. May be involved in the transmission of light information from the retina to the hypothalamus. Modulates cell surface expression of NETO2 (By similarity). Publication Abstract from PubMed Kainate receptors (KARs) are tetrameric, ligand-gated ion channels of the ionotropic glutamate receptor family that mediate excitatory neurotransmission and modulate neuronal circuits and synaptic plasticity during development of the central nervous system. KARs are implicated in psychiatric and neurological diseases and represent a target of therapeutic intervention. Native KARs form complexes with neuropilin and tolloid-like auxiliary subunits (Neto1 and Neto2), which modulate their function, trafficking and synaptic localization. Here we present structures of rat GluK2 KAR in the apo closed state and in the open states activated by agonist kainate and positive allosteric modulator BPAM344, solved in the presence and absence of Neto2 using time-resolved cryo-electron microscopy. While the binding of Neto2 does not change the behavior of individual or dimeric ligand-binding domains (LBDs) or the ion channel, it prevents tightening of the interface between two LBD dimers during activation and slows the kinetics of deactivation. Our structures illuminate the mechanism of KAR activation and its modulation by Neto2. Activation of kainate receptor GluK2-Neto2 complex.,Gangwar SP, Yelshanskaya MV, Yen LY, Newton TP, Sobolevsky AI Nat Struct Mol Biol. 2025 Aug 22. doi: 10.1038/s41594-025-01656-9. PMID:40846810 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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