title: Novel class of spider toxin: active principle from the yellow sac spider Cheiracanthium punctorium venom is a unique two-domain polypeptide.
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.
authors.affiliation: M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Vassilevski
authors.forename: Irina M
authors.initials: IM
authors.lastname: Fedorova
authors.forename: Ekaterina E
authors.initials: EE
authors.lastname: Maleeva
authors.forename: Yuliya V
authors.initials: YV
authors.lastname: Korolkova
authors.forename: Svetlana S
authors.initials: SS
authors.lastname: Efimova
authors.forename: Olga V
authors.initials: OV
authors.lastname: Samsonova
authors.forename: Ludmila V
authors.initials: LV
authors.lastname: Schagina
authors.forename: Alexei V
authors.initials: AV
authors.lastname: Feofanov
authors.forename: Lev G
authors.initials: LG
authors.lastname: Magazanik
authors.forename: Eugene V
authors.initials: EV
authors.lastname: Grishin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D008969:Molecular Sequence Data; D009469:Neuromuscular Junction / Q000187:drug effects; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D017433:Protein Structure, Secondary; D011898:Ranidae; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013111:Spider Venoms / Q000737:chemistry* / Q000145:classification* / Q000235:genetics / Q000494:pharmacology; D013112:Spiders / Q000033:anatomy & histology / Q000737:chemistry*
chemical_list: D010455:Peptides; D013111:Spider Venoms