8xlk

Structure of native tri-heteromeric GluN1-GluN2A-GluN2B NMDA receptor in rat cortex and hippocampus

spinqualitylabelsall models 8xlk, resolution 4.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8xlk is a 12 chain structure with sequence from Mus musculoides and Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 4.2Å Ligands: 7RC, MAN, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function NMDZ1_RAT NMDA receptor subtype of glutamate-gated ion channels possesses high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine. Plays a key role in synaptic plasticity, synaptogenesis, excitotoxicity, memory acquisition and learning. It mediates neuronal functions in glutamate neurotransmission. Is involved in the cell surface targeting of NMDA receptors. Publication Abstract from PubMed The cerebral cortex and hippocampus are crucial brain regions for learning and memory, which depend on activity-induced synaptic plasticity involving N-methyl-á´ -aspartate receptors (NMDARs). However, subunit assembly and molecular architecture of endogenous NMDARs (eNMDARs) in the brain remain elusive. Using conformation- and subunit-dependent antibodies, we purified eNMDARs from adult rat cerebral cortex and hippocampus. Three major subtypes of GluN1-N2A-N2B, GluN1-N2B, and GluN1-N2A eNMDARs were resolved by cryoelectron microscopy (cryo-EM) at the resolution up to 4.2 A. The particle ratio of these three subtypes was 9:7:4, indicating that about half of GluN2A and GluN2B subunits are incorporated into the tri-heterotetramers. Structural analysis revealed the asymmetric architecture of the GluN1-N2A-N2B receptor throughout the extracellular to the transmembrane layers. Moreover, the conformational variations between GluN1-N2B and GluN1-N2A-N2B receptors revealed the distinct biophysical properties across different eNMDAR subtypes. Our findings imply the structural and functional complexity of eNMDARs and shed light on structure-based therapeutic design targeting these eNMDARs in vivo. Assembly and architecture of endogenous NMDA receptors in adult cerebral cortex and hippocampus.,Zhang M, Feng J, Xie C, Song N, Jin C, Wang J, Zhao Q, Zhang L, Wang B, Sun Y, Guo F, Li Y, Zhu S Cell. 2025 Jan 17:S0092-8674(25)00033-9. doi: 10.1016/j.cell.2025.01.004. PMID:39855198 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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