ArticleProceedings of the National Academy of Sciences of the United States of America2013
Crystallographic insights into sodium-channel modulation by the β4 subunit.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 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.
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Who cites it
54 citing papers in PubMed, 80 citations in OpenAlex.
- Nav1.8 and Chronic Pain: From Laboratory Animals to Clinical Patients.Biomolecules · 2025Review
- Sodium Channel β Subunits-An Additional Element in Animal Tetrodotoxin Resistance?International journal of molecular sciences · 2024Article
- Molecular determinants of resurgent sodium currents mediated by Navβ4 peptide and A-type FHFs.Frontiers in molecular neuroscience · 2024Article
- Differential expression of slow and fast-repriming tetrodotoxin-sensitive sodium currents in dorsal root ganglion neurons.Frontiers in molecular neuroscience · 2023Article
- The AMIGO1 adhesion protein activates Kv2.1 voltage sensors.Biophysical journal · 2022Article
- Poly-dipeptides produced fromProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Structural Advances in Voltage-Gated Sodium Channels.Frontiers in pharmacology · 2022Review
- The Voltage-Gated Sodium Channel Beta4 Subunit Maintains Epithelial Phenotype in Mammary Cells.Cells · 2021Article
- Biophysical Investigation of Sodium Channel Interaction with β-Subunit Variants Associated with Arrhythmias.Bioelectricity · 2020Article
- Chemometric Models of Differential Amino Acids at the NaMolecules (Basel, Switzerland) · 2020Article
- Cell-Adhesion Properties of β-Subunits in the Regulation of Cardiomyocyte Sodium Channels.Biomolecules · 2020Review
- Transcriptome profiling of venom gland from wasp species: de novo assembly, functional annotation, and discovery of molecular markers.BMC genomics · 2020Article
- Epilepsy-Related Voltage-Gated Sodium Channelopathies: A Review.Frontiers in pharmacology · 2020Review
- Challenges and Opportunities for Therapeutics Targeting the Voltage-Gated Sodium Channel Isoform NaJournal of medicinal chemistry · 2019Review
- Crystal structures of CaProceedings of the National Academy of Sciences of the United States of America · 2019Article
- Wireless control of cellular function by activation of a novel protein responsive to electromagnetic fields.Scientific reports · 2018Article
- Using voltage-sensor toxins and their molecular targets to investigate NaThe Journal of physiology · 2018Review
- Cross-kingdom auxiliary subunit modulation of a voltage-gated sodium channel.The Journal of biological chemistry · 2018Article
- Voltage-gated sodium channel β subunits: The power outside the pore in brain development and disease.Neuropharmacology · 2018Review
- The voltage-gated sodium channel EF-hands form an interaction with the III-IV linker that is disturbed by disease-causing mutations.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Voltage-gated sodium (Nav) channels are embedded in a multicomponent membrane signaling complex that plays a crucial role in cellular excitability. Although the mechanism remains unclear, β-subunits modify Nav channel function and cause debilitating disorders when mutated. While investigating whether β-subunits also influence ligand interactions, we found that β4 dramatically alters toxin binding to Nav1.2. To explore these observations further, we solved the crystal structure of the extracellular β4 domain and identified (58)Cys as an exposed residue that, when mutated, eliminates the influence of β4 on toxin pharmacology. Moreover, our results suggest the presence of a docking site that is maintained by a cysteine bridge buried within the hydrophobic core of β4. Disrupting this bridge by introducing a β1 mutation implicated in epilepsy repositions the (58)Cys-containing loop and disrupts β4 modulation of Nav1.2. Overall, the principles emerging from this work (i) help explain tissue-dependent variations in Nav channel pharmacology; (ii) enable the mechanistic interpretation of β-subunit-related disorders; and (iii) provide insights in designing molecules capable of correcting aberrant β-subunit behavior.
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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.