5ipr
From Proteopedia
Cryo-EM structure of GluN1/GluN2B NMDA receptor in the DCKA/D-APV-bound conformation, state 3
Structural highlights
FunctionNMDZ1_XENLA Component of NMDA receptor complexes that function as heterotetrameric, ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Channel activation requires binding of the neurotransmitter glutamate to the epsilon subunit, glycine binding to the zeta subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+) (PubMed:16214956, PubMed:19524674, PubMed:21677647, PubMed:25008524, PubMed:26912815, PubMed:27135925, Ref.11, PubMed:28232581). Sensitivity to glutamate and channel kinetics depend on the subunit composition (Probable).[1] [2] [3] [4] [5] [6] [7] [PDB:5IOV] Publication Abstract from PubMedN-methyl-D-aspartate receptors (NMDARs) are glutamate-gated, calcium-permeable ion channels that mediate synaptic transmission and underpin learning and memory. NMDAR dysfunction is directly implicated in diseases ranging from seizure to ischemia. Despite its fundamental importance, little is known about how the NMDAR transitions between inactive and active states and how small molecules inhibit or activate ion channel gating. Here, we report electron cryo-microscopy structures of the GluN1-GluN2B NMDA receptor in an ensemble of competitive antagonist-bound states, an agonist-bound form, and a state bound with agonists and the allosteric inhibitor Ro25-6981. Together with double electron-electron resonance experiments, we show how competitive antagonists rupture the ligand binding domain (LBD) gating "ring," how agonists retain the ring in a dimer-of-dimers configuration, and how allosteric inhibitors, acting within the amino terminal domain, further stabilize the LBD layer. These studies illuminate how the LBD gating ring is fundamental to signal transduction and gating in NMDARs. Mechanism of NMDA Receptor Inhibition and Activation.,Zhu S, Stein RA, Yoshioka C, Lee CH, Goehring A, Mchaourab HS, Gouaux E Cell. 2016 Apr 21;165(3):704-14. doi: 10.1016/j.cell.2016.03.028. Epub 2016 Apr, 7. PMID:27062927[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Large Structures | Xenopus laevis | Goehring A | Gouaux E | Lee CH | Mchaourab SH | Stein AR | Yoshioka C | Zhu S
