ArticleScience (New York, N.Y.)2014
X-ray structures of AMPA receptor-cone snail toxin complexes illuminate activation mechanism.
Article in Science (New York, N.Y.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed.
- Pre-activation and gating pathway of AMPA receptors revealed by full and partial agonists.Nature structural & molecular biology · 2026Article
- The AMPA receptor life cycle: assembly, regulation and synaptic diversity.Nature reviews. Neuroscience · 2026Review
- Structures of partially occupied hetero-tetramers provide insight into kainate receptor activation and desensitization.Nature communications · 2026Article
- Rescuing Neurodevelopmental Deficits in AMPA Receptor Gain-of-Function Mutant.bioRxiv : the preprint server for biology · 2025Article
- GluA4 AMPA receptor gating mechanisms and modulation by auxiliary proteins.Nature structural & molecular biology · 2025Article
- Atomistic mechanisms of calcium permeation modulated by Q/R editing and selectivity filter mutations in GluA2 AMPA receptors.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Positive AMPA and Kainate Receptor Modulators and Their Therapeutic Potential in CNS Diseases: A Comprehensive Review.International journal of molecular sciences · 2025Review
- The proteotranscriptomic characterization of venom in the white seafanOpen biology · 2025Article
- Article
- A genetically encoded secreted toxin potentiates synaptic NMDA receptors in hippocampal neurons and confers neuroprotection.PNAS nexus · 2025Article
- Allosteric competition and inhibition in AMPA receptors.Nature structural & molecular biology · 2024Article
- Temperature Sensitive Glutamate Gating of AMPA-subtype iGluRs.bioRxiv : the preprint server for biology · 2024Article
- High-resolution crystal structure of the Mu8.1 conotoxin from Conus mucronatus.Acta crystallographica. Section F, Structural biology communications · 2023Article
- A previously unrecognized superfamily of macro-conotoxins includes an inhibitor of the sensory neuron calcium channel Cav2.3.PLoS biology · 2023Article
- Fluorescence-Detection Size-Exclusion Chromatography-Based Thermostability Assay for Membrane Proteins.Methods in molecular biology (Clifton, N.J.) · 2023Article
- The action of Con-ikot-ikot toxin on single AMPA-type glutamate receptors.The Journal of general physiology · 2022Article
- Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels.Pharmacological reviews · 2021Review
- Clustered mutations in the GRIK2 kainate receptor subunit gene underlie diverse neurodevelopmental disorders.American journal of human genetics · 2021Article
- AMPA receptor structure and auxiliary subunits.The Journal of physiology · 2021Review
- An improved fluorescent tag and its nanobodies for membrane protein expression, stability assay, and purification.Communications biology · 2020Article
19 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors.
Funding
Abstract
AMPA-sensitive glutamate receptors are crucial to the structural and dynamic properties of the brain, to the development and function of the central nervous system, and to the treatment of neurological conditions from depression to cognitive impairment. However, the molecular principles underlying AMPA receptor activation have remained elusive. We determined multiple x-ray crystal structures of the GluA2 AMPA receptor in complex with a Conus striatus cone snail toxin, a positive allosteric modulator, and orthosteric agonists, at 3.8 to 4.1 angstrom resolution. We show how the toxin acts like a straightjacket on the ligand-binding domain (LBD) "gating ring," restraining the domains via both intra- and interdimer cross-links such that agonist-induced closure of the LBD "clamshells" is transduced into an irislike expansion of the gating ring. By structural analysis of activation-enhancing mutants, we show how the expansion of the LBD gating ring results in pulling forces on the M3 helices that, in turn, are coupled to ion channel gating.
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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.