8e92
From Proteopedia
D-cycloserine and glutamate bound Human GluN1a-GluN2C NMDA receptor in intact conformation
Structural highlights
DiseaseNMDZ1_HUMAN Defects in GRIN1 are the cause of mental retardation autosomal dominant type 8 (MRD8) [MIM:614254. Mental retardation is characterized by significantly below average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period.[1] FunctionNMDZ1_HUMAN NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine. This protein 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 (By similarity). Publication Abstract from PubMedNeurotransmission mediated by diverse subtypes of N-methyl-D-aspartate receptors (NMDARs) is fundamental for basic brain functions and development as well as neuropsychiatric diseases and disorders. NMDARs are glycine- and glutamate-gated ion channels that exist as heterotetramers composed of obligatory GluN1 and GluN2(A-D) and/or GluN3(A-B). The GluN2C and GluN2D subunits form ion channels with distinct properties and spatio-temporal expression patterns. Here, we provide the structures of the agonist-bound human GluN1-2C NMDAR in the presence and absence of the GluN2C-selective positive allosteric potentiator (PAM), PYD-106, the agonist-bound GluN1-2A-2C tri-heteromeric NMDAR, and agonist-bound GluN1-2D NMDARs by single-particle electron cryomicroscopy. Our analysis shows unique inter-subunit and domain arrangements of the GluN2C NMDARs, which contribute to functional regulation and formation of the PAM binding pocket and is distinct from GluN2D NMDARs. Our findings here provide the fundamental blueprint to study GluN2C- and GluN2D-containing NMDARs, which are uniquely involved in neuropsychiatric disorders. , PMID:36309015[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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