ArticleProceedings of the National Academy of Sciences of the United States of America2011
Mapping the receptor site for alpha-scorpion toxins on a Na+ channel voltage sensor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 67 papers.
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
67 citing papers in PubMed, 128 citations in OpenAlex.
- A structural atlas of druggable sites on NaChannels (Austin, Tex.) · 2024Review
- δ-Conotoxin Structure Prediction and Analysis through Large-Scale Comparative and Deep Learning Modeling Approaches.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Voltage gated sodium and calcium channels: Discovery, structure, function, and Pharmacology.Channels (Austin, Tex.) · 2023Review
- Molecular determinants of inhibition of the human proton channel hHv1 by the designer peptide C6 and a bivalent derivative.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Allosteric interactions among voltage-sensor modules of sodium channels probed by scorpion toxin modifiers.Journal of neurobiology and physiology · 2022Article
- Molecular mechanism of the spider toxin κ-LhTx-I acting on the bacterial voltage-gated sodium channel NaChBac.Frontiers in pharmacology · 2022Article
- Charge substitutions at the voltage-sensing module of domain III enhance actions of site-3 and site-4 toxins on an insect sodium channel.Insect biochemistry and molecular biology · 2021Article
- Structural basis for voltage-sensor trapping of the cardiac sodium channel by a deathstalker scorpion toxin.Nature communications · 2021Article
- Critical Role of E1623 Residue in S3-S4 Loop of Nav1.1 Channel and Correlation Between Nature of Substitution and Functional Alteration.Frontiers in molecular neuroscience · 2021Article
- Article
- Venoms of Iranian Scorpions (Arachnida, Scorpiones) and Their Potential for Drug Discovery.Molecules (Basel, Switzerland) · 2019Review
- Review
- BmK AEP, an Anti-Epileptic Peptide Distinctly Affects the Gating of Brain Subtypes of Voltage-Gated Sodium Channels.International journal of molecular sciences · 2019Article
- Scorpion Toxins: Positive Selection at a Distal Site Modulates Functional Evolution at a Bioactive Site.Molecular biology and evolution · 2019Article
- Role of human Hv1 channels in sperm capacitation and white blood cell respiratory burst established by a designed peptide inhibitor.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- PF-06526290 can both enhance and inhibit conduction through voltage-gated sodium channels.British journal of pharmacology · 2018Article
- Predicting Structural Details of the Sodium Channel Pore Basing on Animal Toxin Studies.Frontiers in pharmacology · 2018Review
- Discovery of peptide ligands through docking and virtual screening at nicotinic acetylcholine receptor homology models.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Structural Insights into the Atomistic Mechanisms of Action of Small Molecule Inhibitors Targeting the KCa3.1 Channel Pore.Molecular pharmacology · 2017Article
- The Molecular Basis of Toxins' Interactions with Intracellular Signaling via Discrete Portals.Toxins · 2017Review
7 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
The α-scorpions toxins bind to the resting state of Na(+) channels and inhibit fast inactivation by interaction with a receptor site formed by domains I and IV. Mutants T1560A, F1610A, and E1613A in domain IV had lower affinities for Leiurus quinquestriatus hebraeus toxin II (LqhII), and mutant E1613R had ~73-fold lower affinity. Toxin dissociation was accelerated by depolarization and increased by these mutations, whereas association rates at negative membrane potentials were not changed. These results indicate that Thr1560 in the S1-S2 loop, Phe1610 in the S3 segment, and Glu1613 in the S3-S4 loop in domain IV participate in toxin binding. T393A in the SS2-S6 loop in domain I also had lower affinity for LqhII, indicating that this extracellular loop may form a secondary component of the receptor site. Analysis with the Rosetta-Membrane algorithm resulted in a model of LqhII binding to the voltage sensor in a resting state, in which amino acid residues in an extracellular cleft formed by the S1-S2 and S3-S4 loops in domain IV interact with two faces of the wedge-shaped LqhII molecule. The conserved gating charges in the S4 segment are in an inward position and form ion pairs with negatively charged amino acid residues in the S2 and S3 segments of the voltage sensor. This model defines the structure of the resting state of a voltage sensor of Na(+) channels and reveals its mode of interaction with a gating modifier toxin.
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What Socratic holds
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 Socratic graph.