ArticleThe Journal of biological chemistry2009
Molecular requirements for recognition of brain voltage-gated sodium channels by scorpion alpha-toxins.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Purification and Molecular Characterization of a Mammalian Neurotoxin as a Pharmaceutical Tool from the Venom of Iranian ScorpionJournal of arthropod-borne diseases · 2024Article
- Allosteric interactions among voltage-sensor modules of sodium channels probed by scorpion toxin modifiers.Journal of neurobiology and physiology · 2022Article
- Protein surface topography as a tool to enhance the selective activity of a potassium channel blocker.The Journal of biological chemistry · 2019Article
- Scorpion Toxins: Positive Selection at a Distal Site Modulates Functional Evolution at a Bioactive Site.Molecular biology and evolution · 2019Article
- Target-Driven Evolution of Scorpion Toxins.Scientific reports · 2015Article
- Wheat germ in vitro translation to produce one of the most toxic sodium channel specific toxins.Bioscience reports · 2014Article
- Article
- Scorpion venom components that affect ion-channels function.Toxicon : official journal of the International Society on Toxinology · 2013Review
- Structure and function of hainantoxin-III, a selective antagonist of neuronal tetrodotoxin-sensitive voltage-gated sodium channels isolated from the Chinese bird spider Ornithoctonus hainana.The Journal of biological chemistry · 2013Article
- Modular organization of α-toxins from scorpion venom mirrors domain structure of their targets, sodium channels.The Journal of biological chemistry · 2013Article
- Computational methods of studying the binding of toxins from venomous animals to biological ion channels: theory and applications.Physiological reviews · 2013Review
- The role of glycine residues at the C-terminal peptide segment in antinociceptive activity: a molecular dynamics simulation.Journal of molecular modeling · 2013Article
- Direct evidence that scorpion α-toxins (site-3) modulate sodium channel inactivation by hindrance of voltage-sensor movements.PloS one · 2013Article
- Solution structure of kurtoxin: a gating modifier selective for Cav3 voltage-gated Ca(2+) channels.Biochemistry · 2012Article
- Evolutionary diversification of Mesobuthus α-scorpion toxins affecting sodium channels.Molecular & cellular proteomics : MCP · 2012Article
- Elucidation of the molecular basis of selective recognition uncovers the interaction site for the core domain of scorpion alpha-toxins on sodium channels.The Journal of biological chemistry · 2011Article
- Mapping the receptor site for alpha-scorpion toxins on a Na+ channel voltage sensor.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Common molecular determinants of tarantula huwentoxin-IV inhibition of Na+ channel voltage sensors in domains II and IV.The Journal of biological chemistry · 2011Article
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8 authors.
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Abstract
The scorpion alpha-toxin Lqh2 (from Leiurus quinquestriatus hebraeus) is active at various mammalian voltage-gated sodium channels (Na(v)s) and is inactive at insect Na(v)s. To resolve the molecular basis of this preference we used the following strategy: 1) Lqh2 was expressed in recombinant form and key residues important for activity at the rat brain channel rNa(v)1.2a were identified by mutagenesis. These residues form a bipartite functional surface made of a conserved "core domain" (residues of the loops connecting the secondary structure elements of the molecule core), and a variable "NC domain" (five-residue turn and the C-tail) as was reported for other scorpion alpha-toxins. 2) The functional role of the two domains was validated by their stepwise construction on the similar scaffold of the anti-insect toxin LqhalphaIT. Analysis of the activity of the intermediate constructs highlighted the critical role of Phe(15) of the core domain in toxin potency at rNa(v)1.2a, and has suggested that the shape of the NC-domain is important for toxin efficacy. 3) Based on these findings and by comparison with other scorpion alpha-toxins we were able to eliminate the activity of Lqh2 at rNa(v)1.4 (skeletal muscle), hNa(v)1.5 (cardiac), and rNa(v)1.6 channels, with no hindrance of its activity at Na(v)1.1-1.3. These results suggest that by employing a similar approach the design of further target-selective sodium channel modifiers is imminent.
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