ArticleNature communications2021
Conformational rearrangement of the NMDA receptor amino-terminal domain during activation and allosteric modulation.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
- Inhibition of delta-1 glutamate receptor current by extracellular protons.bioRxiv : the preprint server for biology · 2026Article
- Ligand Binding Dynamics of Ion Channels and GPCRs Using Single-Molecule Fluorescence.Annual review of biophysics · 2026Review
- Polarity-determined triple partition of dual binding pockets unlocks mechanistic insights and a novel antagonist design of NMDA receptors: a combined MD/DFT study.RSC advances · 2026Article
- Scales of Postsynaptic Nanostructure: Molecules, Nanoclusters, and Nanodomains.Advances in neurobiology · 2026Review
- Domain coupling in activation of a family C GPCR.Nature chemical biology · 2025Article
- Design of (Journal of medicinal chemistry · 2025Article
- A genetically encoded secreted toxin potentiates synaptic NMDA receptors in hippocampal neurons and confers neuroprotection.PNAS nexus · 2025Article
- Regulation of NMDAR activation efficiency by environmental factors and subunit composition.The Journal of general physiology · 2025Article
- Subtype-specific conformational landscape of NMDA receptor gating.Cell reports · 2024Article
- Single-Molecule Imaging of Integral Membrane Protein Dynamics and Function.Annual review of biophysics · 2024Review
- 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
- Single-Molecule FRET Analyses of NMDA Receptors.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Structural insights into NMDA receptor pharmacology.Biochemical Society transactions · 2023Review
- Ion flux-independent NMDA receptor signaling.Neuropharmacology · 2022Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
N-Methyl-D-aspartate receptors (NMDARs) are ionotropic glutamate receptors essential for synaptic plasticity and memory. Receptor activation involves glycine- and glutamate-stabilized closure of the GluN1 and GluN2 subunit ligand binding domains that is allosterically regulated by the amino-terminal domain (ATD). Using single molecule fluorescence resonance energy transfer (smFRET) to monitor subunit rearrangements in real-time, we observe a stable ATD inter-dimer distance in the Apo state and test the effects of agonists and antagonists. We find that GluN1 and GluN2 have distinct gating functions. Glutamate binding to GluN2 subunits elicits two identical, sequential steps of ATD dimer separation. Glycine binding to GluN1 has no detectable effect, but unlocks the receptor for activation so that glycine and glutamate together drive an altered activation trajectory that is consistent with ATD dimer separation and rotation. We find that protons exert allosteric inhibition by suppressing the glutamate-driven ATD separation steps, and that greater ATD separation translates into greater rotation and higher open probability.
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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.