negative regulation of dendritic spine development / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration / EPHB-mediated forward signaling / Assembly and cell surface presentation of NMDA receptors / olfactory learning / conditioned taste aversion / dendritic branch / regulation of respiratory gaseous exchange ...negative regulation of dendritic spine development / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration / EPHB-mediated forward signaling / Assembly and cell surface presentation of NMDA receptors / olfactory learning / conditioned taste aversion / dendritic branch / regulation of respiratory gaseous exchange / protein localization to postsynaptic membrane / propylene metabolic process / response to glycine / voltage-gated monoatomic cation channel activity / regulation of monoatomic cation transmembrane transport / response to morphine / glutamate receptor activity / Assembly and cell surface presentation of NMDA receptors / NMDA glutamate receptor activity / Synaptic adhesion-like molecules / RAF/MAP kinase cascade / NMDA selective glutamate receptor complex / glutamate-gated calcium ion channel activity / parallel fiber to Purkinje cell synapse / calcium ion transmembrane import into cytosol / protein heterotetramerization / glutamate binding / positive regulation of reactive oxygen species biosynthetic process / neuromuscular process / regulation of synapse assembly / glycine binding / positive regulation of calcium ion transport into cytosol / regulation of dendrite morphogenesis / male mating behavior / regulation of axonogenesis / suckling behavior / startle response / monoatomic cation transmembrane transport / dendrite development / regulation of neuronal synaptic plasticity / response to amine / social behavior / associative learning / positive regulation of excitatory postsynaptic potential / monoatomic cation transport / ligand-gated monoatomic ion channel activity / excitatory synapse / cellular response to glycine / positive regulation of dendritic spine maintenance / Unblocking of NMDA receptors, glutamate binding and activation / phosphatase binding / glutamate receptor binding / calcium ion homeostasis / cellular response to manganese ion / prepulse inhibition / long-term memory / monoatomic cation channel activity / regulation of neuron apoptotic process / presynaptic active zone membrane / synaptic cleft / glutamate-gated receptor activity / response to fungicide / sensory perception of pain / dendrite membrane / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / response to amphetamine / presynaptic modulation of chemical synaptic transmission / ionotropic glutamate receptor signaling pathway / excitatory postsynaptic potential / hippocampal mossy fiber to CA3 synapse / positive regulation of synaptic transmission, glutamatergic / adult locomotory behavior / protein phosphatase 2A binding / synaptic membrane / learning / synaptic transmission, glutamatergic / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / regulation of membrane potential / postsynaptic density membrane / regulation of long-term neuronal synaptic plasticity / calcium channel activity / regulation of synaptic plasticity / visual learning / modulation of chemical synaptic transmission / response to organic cyclic compound / terminal bouton / cerebral cortex development / memory / synaptic vesicle membrane / response to calcium ion / intracellular calcium ion homeostasis / neuron cellular homeostasis / calcium ion transport / rhythmic process / synaptic vesicle / presynapse / presynaptic membrane / signaling receptor activity / amyloid-beta binding / chemical synaptic transmission Similarity search - Function
: / : / Bacterial extracellular solute-binding proteins, family 3 / Solute-binding protein family 3/N-terminal domain of MltF / Ionotropic glutamate receptor, metazoa / Ligated ion channel L-glutamate- and glycine-binding site / : / Ligand-gated ion channel / Ionotropic glutamate receptor, L-glutamate and glycine-binding domain / Ligated ion channel L-glutamate- and glycine-binding site ...: / : / Bacterial extracellular solute-binding proteins, family 3 / Solute-binding protein family 3/N-terminal domain of MltF / Ionotropic glutamate receptor, metazoa / Ligated ion channel L-glutamate- and glycine-binding site / : / Ligand-gated ion channel / Ionotropic glutamate receptor, L-glutamate and glycine-binding domain / Ligated ion channel L-glutamate- and glycine-binding site / Ionotropic glutamate receptor / Eukaryotic homologues of bacterial periplasmic substrate binding proteins. / Receptor, ligand binding region / Receptor family ligand binding region / Periplasmic binding protein-like I Similarity search - Domain/homology
National Institutes of Health/National Institute of Mental Health (NIH/NIMH)
NS11745,
United States
National Institutes of Health/National Institute of Mental Health (NIH/NIMH)
MH085926
United States
National Institutes of Health/National Institute of Mental Health (NIH/NIMH)
F32MH121061
United States
National Institutes of Health/National Institute of Mental Health (NIH/NIMH)
NS113632
United States
Citation
Journal: Sci Adv / Year: 2024 Title: Structure and function of GluN1-3A NMDA receptor excitatory glycine receptor channel. Authors: Kevin Michalski / Hiro Furukawa / Abstract: -methyl-d-aspartate receptors (NMDARs) and other ionotropic glutamate receptors (iGluRs) mediate most of the excitatory signaling in the mammalian brains in response to the neurotransmitter glutamate. ...-methyl-d-aspartate receptors (NMDARs) and other ionotropic glutamate receptors (iGluRs) mediate most of the excitatory signaling in the mammalian brains in response to the neurotransmitter glutamate. Uniquely, NMDARs composed of GluN1 and GluN3 are activated exclusively by glycine, the neurotransmitter conventionally mediating inhibitory signaling when it binds to pentameric glycine receptors. The GluN1-3 NMDARs are vital for regulating neuronal excitability, circuit function, and specific behaviors, yet our understanding of their functional mechanism at the molecular level has remained limited. Here, we present cryo-electron microscopy structures of GluN1-3A NMDARs bound to an antagonist, CNQX, and an agonist, glycine. The structures show a 1-3-1-3 subunit heterotetrameric arrangement and an unprecedented pattern of GluN3A subunit orientation shift between the glycine-bound and CNQX-bound structures. Site-directed disruption of the unique subunit interface in the glycine-bound structure mitigated desensitization. Our study provides a foundation for understanding the distinct structural dynamics of GluN3 that are linked to the unique function of GluN1-3 NMDARs.
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