ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010
NMDA receptors with locked glutamate-binding clefts open with high efficacy.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 40 citations in OpenAlex.
- Novel binding mode for negative allosteric NMDA receptor modulators.The Journal of general physiology · 2026Article
- Distinct Regulation of Early Trafficking of the NMDA Receptors by the Ligand-Binding Domains of the GluN1 and GluN2A Subunits.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Evaluation of allosteric N-methyl-d-aspartate receptor modulation by GluN2A-selective antagonists using pharmacological equilibrium modeling.Molecular pharmacology · 2025Article
- Mechanistic and structural studies reveal NRAP-1-dependent coincident activation of NMDARs.Cell reports · 2024Article
- Hodgkin-Huxley-Katz Prize Lecture: Genetic and pharmacological control of glutamate receptor channel through a highly conserved gating motif.The Journal of physiology · 2020Article
- Glutamate and Glycine Binding to the NMDA Receptor.Structure (London, England : 1993) · 2018Article
- Mechanism and properties of positive allosteric modulation of N-methyl-d-aspartate receptors by 6-alkyl 2-naphthoic acid derivatives.Neuropharmacology · 2017Article
- A single-channel mechanism for pharmacological potentiation of GluN1/GluN2A NMDA receptors.Scientific reports · 2017Article
- Probing the Structural Dynamics of the NMDA Receptor Activation by Coarse-Grained Modeling.Biophysical journal · 2017Article
- Gating Motions and Stationary Gating Properties of Ionotropic Glutamate Receptors: Computation Meets Electrophysiology.Accounts of chemical research · 2017Review
- Allosteric Interactions between NMDA Receptor Subunits Shape the Developmental Shift in Channel Properties.Neuron · 2017Article
- NMDA receptors: linking physiological output to biophysical operation.Nature reviews. Neuroscience · 2017Review
- Mechanism of partial agonism in AMPA-type glutamate receptors.Nature communications · 2017Article
- Differential effects of TM4 tryptophan mutations on inhibition of N-methyl-d-aspartate receptors by ethanol and toluene.Alcohol (Fayetteville, N.Y.) · 2016Article
- Semiclosed Conformations of the Ligand-Binding Domains of NMDA Receptors during Stationary Gating.Biophysical journal · 2016Article
- Structural Basis for Negative Allosteric Modulation of GluN2A-Containing NMDA Receptors.Neuron · 2016Article
- Protons Potentiate GluN1/GluN3A Currents by Attenuating Their Desensitisation.Scientific reports · 2016Article
- Kinetic contributions to gating by interactions unique to N-methyl-D-aspartate (NMDA) receptors.The Journal of biological chemistry · 2015Article
- The differential contribution of GluN1 and GluN2 to the gating operation of the NMDA receptor channel.Pflugers Archiv : European journal of physiology · 2015Article
- Conformational transitions in the glycine-bound GluN1 NMDA receptor LBD via single-molecule FRET.Biophysical journal · 2015Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Glutamate-gated channels mediate fundamental brain processes, yet the mechanisms by which the neurotransmitter controls channel activation are incompletely understood. Structural studies revealed that the agonist has the critical role of bridging the divide between two flexible extracellular lobes and solidified the view that agonist-induced cleft-closure drives further isomerizations, which eventually open the channel. Within the glutamate receptor family, NMDA-sensitive channels are unique in their requirement that both glycine and glutamate bind to homologous regions on GluN1 and GluN2 subunits, respectively, before the channel can open. To study the gating reaction in separation from agonist binding and dissociation, we characterized the kinetic mechanism of individual NMDA receptors whose ligand-binding clefts were locked shut by disulfide bridges engineered across lobes. We found that locking GluN1 domains had no observable consequences on receptor activity, whereas locking GluN2A domains increased channel activity without reducing the number of resolvable kinetic states. Based on these results, we suggest that glutamate but not glycine activates NMDA receptors with submaximal efficacy. Low glutamate efficacy may represent a mechanism by which the neurotransmitter maintains control over receptor kinetics despite sharing with glycine the task of activation.
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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.