ArticleNeuron2018
Neurotransmitter Funneling Optimizes Glutamate Receptor Kinetics.
Article in Neuron, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Voltage-sensor conformational microenvironments encode isoform-selective ion channel activation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Serotonergic Signaling Rewired: A Lipid Raft-Controlled Model of Synaptic Transmission Grounded in the Fundamental Parameters of Biological Systems.Life (Basel, Switzerland) · 2026Article
- The molecular mechanisms of visual chromophore release from cellular retinaldehyde-binding protein.Structure (London, England : 1993) · 2025Article
- A conifer metabolite corrects episodic ataxia type 1 by voltage sensor-mediated ligand activation of Kv1.1.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- The impact of diffusion on receptor binding during synaptic transmission.Biophysical journal · 2024Article
- Merging Signaling with Structure: Functions and Mechanisms of Plant Glutamate Receptor Ion Channels.Annual review of plant biology · 2023Review
- Article
- Strain and rupture of HIV-1 capsids during uncoating.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels.Pharmacological reviews · 2021Review
- Structural biology and thermodynamics of GluD receptors.Neuropharmacology · 2021Review
- A multiscale coarse-grained model of the SARS-CoV-2 virion.Biophysical journal · 2021Article
- How Energy Supports Our Brain to Yield Consciousness: Insights From Neuroimaging Based on the Neuroenergetics Hypothesis.Frontiers in systems neuroscience · 2021Review
- Atomic-scale characterization of mature HIV-1 capsid stabilization by inositol hexakisphosphate (IPScience advances · 2020Article
- A mechanism for the activation of the mechanosensitive Piezo1 channel by the small molecule Yoda1.Nature communications · 2019Article
- Population Shift Mechanism for Partial Agonism of AMPA Receptor.Biophysical journal · 2019Article
- Glutamate and Glycine Binding to the NMDA Receptor.Structure (London, England : 1993) · 2018Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Ionotropic glutamate receptors (iGluRs) mediate neurotransmission at the majority of excitatory synapses in the brain. Little is known, however, about how glutamate reaches the recessed binding pocket in iGluR ligand-binding domains (LBDs). Here we report the process of glutamate binding to a prototypical iGluR, GluA2, in atomistic detail using unbiased molecular simulations. Charged residues on the LBD surface form pathways that facilitate glutamate binding by effectively reducing a three-dimensional diffusion process to a spatially constrained, two-dimensional one. Free energy calculations identify residues that metastably bind glutamate and help guide it into the binding pocket. These simulations also reveal that glutamate can bind in an inverted conformation and also reorient while in its pocket. Electrophysiological recordings demonstrate that eliminating these transient binding sites slows activation and deactivation, consistent with slower glutamate binding and unbinding. These results suggest that binding pathways have evolved to optimize rapid responses of AMPA-type iGluRs at synapses.
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Registered trials
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