ArticleProteins2018
The GluN2B-Glu413Gly NMDA receptor variant arising from a de novo GRIN2B mutation promotes ligand-unbinding and domain opening.
Article in Proteins, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
- Disease-Associated Variants in GRIN1, GRIN2A and GRIN2B genes: Insights into NMDA Receptor Structure, Function, and Pathophysiology.Physiological research · 2024Review
- Rescuing tri-heteromeric NMDA receptor function: the potential of pregnenolone-sulfate in loss-of-function GRIN2B variants.Cellular and molecular life sciences : CMLS · 2024Article
- Bilateral hearing loss caused by anti-NMDA receptor encephalitis with teratoma: A case report.Ibrain · 2024Article
- N-methyl-D-aspartate receptor hypofunction as a potential contributor to the progression and manifestation of many neurological disorders.Frontiers in molecular neuroscience · 2023Review
- Protein quality control ofFrontiers in cellular neuroscience · 2022Review
- Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels.Pharmacological reviews · 2021Review
- TwoeLife · 2021Article
- A Mechanistic Model of NMDA and AMPA Receptor-Mediated Synaptic Transmission in Individual Hippocampal CA3-CA1 Synapses: A Computational Multiscale Approach.International journal of molecular sciences · 2021Article
- The Extracellular Domains of GluN Subunits Play an Essential Role in Processing NMDA Receptors in the ER.Frontiers in neuroscience · 2021Review
- The pathogenic S688Y mutation in the ligand-binding domain of the GluN1 subunit regulates the properties of NMDA receptors.Scientific reports · 2020Article
- Positive allosteric modulators that target NMDA receptors rectify loss-of-function GRIN variants associated with neurological and neuropsychiatric disorders.Neuropharmacology · 2020Article
- Distinct roles ofF1000Research · 2019Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 2 countries.
Funding
Abstract
N-methyl-D-aspartate (NMDA) receptors are transmembrane glutamate-binding ion channels that mediate neurotransmission in mammals. NMDA receptor subunits are tetrameric complexes of GluN1 and GluN2A-D subunits, encoded by the GRIN gene family. Of these subunits, GluN2B is suggested to be required for normal development of the central nervous system. A mutation identified in a patient with developmental delay, E413G, resides in the GluN2B ligand-binding domain and substantially reduces glutamate potency by an unknown mechanism. GluN2B Gly413, though near the agonist, is not in van der Waals contact with glutamate. Visual analysis of the GluN2B structure with the E413G mutation modeled suggests that replacement of Glu with Gly at this position increases solvent access to the ligand-binding domain. This was confirmed by molecular modeling, which showed that the ligand is more mobile in GluN2B-E413G than WT GluN2B. Evaluation of agonist occupancy using random accelerated molecular dynamics (RAMD) simulations predicts that the glutamate exits the binding-site more rapidly for GluN2B-E413G than WT receptors. This analysis was extended to other binding-site mutations, which produced qualitative agreement between experimentally determined EC
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.