It has been shown recently that polypeptide toxins that modulate the gating properties of voltage-sensitive cation channels are able to bind to phospholipid membranes, leading to the suggestion that these toxins are able to access a channel-binding site that remains membrane-restricted (Lee, S.-Y., and MacKinnon, R. (2004) Nature 430, 232-235). We therefore examined the ability of anthopleurin B (ApB), a sea anemone toxin that selectively modifies inactivation kinetics of Na(V)1.x channels, and ProTx-II, a spider toxin that modifies activation kinetics of the same channels, to bind to liposomes. Whereas ProTx-II can be quantitatively depleted from solution upon incubation with phosphatidylcholine/phosphatidylserine liposomes, ApB displays no discernible phospholipid binding activity. We therefore examined the activities of structurally unrelated site 3 and site 4 toxins derived from Leiurus and Centruroides venoms, respectively, in the same assay. Like ApB, the site 3 toxin LqqV shows no lipid binding activity, whereas the site 4 toxin Centruroides toxin II, like ProTx-II, is completely bound. We conclude that toxins that modify inactivation kinetics via binding to Na(V)1.x site 3 lack the ability to bind phospholipids, whereas site 4 toxins, which modify activation, have this activity. This inherent difference suggests that the conformation of domain II more closely resembles that of the K(V)AP channel than does the conformation of domain IV.
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Nat Commun
January 2025
Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI, 48109, USA.
Bacterial transcription activator-like effectors (TALEs) promote pathogenicity by activating host susceptibility (S) genes. To understand the pathogenicity and host adaptation of Xanthomonas citri pv. malvacearum (Xcm), we assemble the genome and the TALE repertoire of three recent Xcm Texas isolates.
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Plant Pathology Laboratory, School of Plant and Environmental Sciences, Alson H. Smith Jr. Agricultural Research and Extension Center, Virginia Polytechnic Institute and State University, Winchester, Virginia, USA.
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January 2025
Division of Basic Biomedical Sciences, University of South Dakota Sanford School of Medicine, Vermillion, SD 57069, USA.
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View Article and Find Full Text PDFMolecules
January 2025
College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China.
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December 2024
Department of Chemistry & Chemical Biology, The University of New Mexico, Albuquerque, NM 87131, USA.
Tetrodotoxin (TTX), a potent Site-1 sodium channel blocker (S1SCB), offers highly effective local anesthetic properties with minimal addiction potential. To fully leverage TTX's capabilities as a local anesthetic, it is crucial to develop a drug delivery system that balances its systemic toxicity with its therapeutic efficacy. Recent studies have shown that peptide mixtures, derived from fragments of Site-1 sodium channel proteins and enhanced with hydrophobic tails (designated MP1 and MP2), can self-assemble into nanostructures that exhibit remarkable sustained-release capabilities for TTX.
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