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PMID:20657014

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Citation

Vassilevski, AA, Fedorova, IM, Maleeva, EE, Korolkova, YV, Efimova, SS, Samsonova, OV, Schagina, LV, Feofanov, AV, Magazanik, LG and Grishin, EV (2010) Novel class of spider toxin: active principle from the yellow sac spider Cheiracanthium punctorium venom is a unique two-domain polypeptide. J. Biol. Chem. 285:32293-302

Abstract

Venom of the yellow sac spider Cheiracanthium punctorium (Miturgidae) was found unique in terms of molecular composition. Its principal toxic component CpTx 1 (15.1 kDa) was purified, and its full amino acid sequence (134 residues) was established by protein chemistry and mass spectrometry techniques. CpTx 1 represents a novel class of spider toxin with modular architecture. It consists of two different yet homologous domains (modules) each containing a putative inhibitor cystine knot motif, characteristic of the widespread single domain spider neurotoxins. Venom gland cDNA sequencing provided precursor protein (prepropeptide) structures of three CpTx 1 isoforms (a-c) that differ by single residue substitutions. The toxin possesses potent insecticidal (paralytic and lethal), cytotoxic, and membrane-damaging activities. In both fly and frog neuromuscular preparations, it causes stable and irreversible depolarization of muscle fibers leading to contracture. This effect appears to be receptor-independent and is inhibited by high concentrations of divalent cations. CpTx 1 lyses cell membranes, as visualized by confocal microscopy, and destabilizes artificial membranes in a manner reminiscent of other membrane-active peptides by causing numerous defects of variable conductance and leading to bilayer rupture. The newly discovered class of modular polypeptides enhances our knowledge of the toxin universe.

Links

PubMed PMC2952230 Online version:10.1074/jbc.M110.104265

Keywords

Amino Acid Sequence; Animals; Base Sequence; Molecular Sequence Data; Neuromuscular Junction/drug effects; Peptides/chemistry; Peptides/genetics; Peptides/pharmacology; Protein Structure, Secondary; Ranidae; Sequence Alignment; Sequence Homology, Amino Acid; Spider Venoms/chemistry; Spider Venoms/classification; Spider Venoms/genetics; Spider Venoms/pharmacology; Spiders/anatomy & histology; Spiders/chemistry

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

Notes

See also

References

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