ArticleBiophysical journal2013
An NMDA receptor gating mechanism developed from MD simulations reveals molecular details underlying subunit-specific contributions.
Article in Biophysical journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 44 citations in OpenAlex.
- Facilitation of hERG Activation by Its Blocker: A Mechanism to Reduce Drug-Induced Proarrhythmic Risk.International journal of molecular sciences · 2023Review
- Structural biology and thermodynamics of GluD receptors.Neuropharmacology · 2021Review
- From bedside-to-bench: What disease-associated variants are teaching us about the NMDA receptor.The Journal of physiology · 2021Review
- NMDA Receptor Opening and Closing-Transitions of a Molecular Machine Revealed by Molecular Dynamics.Biomolecules · 2019Article
- Activation and desensitization of ionotropic glutamate receptors by selectively triggering pre-existing motions.Neuroscience letters · 2019Review
- An inter-dimer allosteric switch controls NMDA receptor activity.The EMBO journal · 2019Article
- A conserved glycine harboring disease-associated mutations permits NMDA receptor slow deactivation and high CaNature communications · 2018Article
- A structurally derived model of subunit-dependent NMDA receptor function.The Journal of physiology · 2018Article
- Glutamate and Glycine Binding to the NMDA Receptor.Structure (London, England : 1993) · 2018Article
- The LILI Motif of M3-S2 Linkers Is a Component of the NMDA Receptor Channel Gate.Frontiers in molecular neuroscience · 2018Article
- Structural modeling for the open state of an NMDA receptor.Journal of structural biology · 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
- Computationally Discovered Potentiating Role of Glycans on NMDA Receptors.Scientific reports · 2017Article
- NMDA receptors: linking physiological output to biophysical operation.Nature reviews. Neuroscience · 2017Review
- Phylogenetic analysis of ionotropic L-glutamate receptor genes in the Bilateria, with special notes on Aplysia californica.BMC evolutionary biology · 2017Article
- Semiclosed Conformations of the Ligand-Binding Domains of NMDA Receptors during Stationary Gating.Biophysical journal · 2016Article
- The Transmembrane Domain Mediates Tetramerization of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptors.The Journal of biological chemistry · 2016Article
- Mechanism-Based Mathematical Model for Gating of Ionotropic Glutamate Receptors.The journal of physical chemistry. B · 2015Article
- Conformational transitions in the glycine-bound GluN1 NMDA receptor LBD via single-molecule FRET.Biophysical journal · 2015Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
N-methyl-D-aspartate (NMDA) receptors are obligate heterotetrameric ligand-gated ion channels that play critical roles in learning and memory. Here, using targeted molecular dynamics simulations, we developed an atomistic model for the gating of the GluN1/GluN2A NMDA receptor. Upon agonist binding, lobe closure of the ligand-binding domain produced outward pulling of the M3-D2 linkers, leading to outward movements of the C-termini of the pore-lining M3 helices and opening of the channel. The GluN2A subunits, similar to the distal (B/D) subunits in the homotetrameric GluA2 α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate receptor, had greater M3 outward movements and thus contributed more to channel gating than the GluN1 subunits. Our gating model is validated by functional studies, including cysteine modification data indicating wider accessibility to the GluN1 M3 helices than to the GluN2A M3 helices from the lumen of the open channel, and reveals why the Lurcher mutation in GluN1 has a stronger ability in maintaining channel opening than the counterpart in GluN2A. The resulting structural model for the open state provides an explanation for the Ca(2+) permeability of NMDA receptors, and the structural differences between the closed and open states form the basis for drug design.
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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.