title: Cysteine-rich toxins from Lachesana tarabaevi spider venom with amphiphilic C-terminal segments.
abstract: Venom of Lachesana tarabaevi (Zodariidae, "ant spiders") exhibits high insect toxicity and serves a rich source of potential insecticides. Five new peptide toxins active against insects were isolated from the venom by means of liquid chromatography and named latartoxins (LtTx). Complete amino acid sequences of LtTx (60-71 residues) were established by a combination of Edman degradation, mass spectrometry and selective proteolysis. Three toxins have eight cysteine residues that form four intramolecular disulfide bridges, and two other molecules contain an additional cystine; three LtTx are C-terminally amidated. Latartoxins can be allocated to two groups with members similar to CSTX and LSTX toxins from Cupiennius salei (Ctenidae) and Lycosa singoriensis (Lycosidae). The interesting feature of the new toxins is their modular organization: they contain an N-terminal cysteine-rich (knottin or ICK) region as in many neurotoxins from spider venoms and a C-terminal linear part alike some cytolytic peptides. The C-terminal fragment of one of the most abundant toxins LtTx-1a was synthesized and shown to possess membrane-binding activity. It was found to assume amphipathic α-helical conformation in membrane-mimicking environment and exert antimicrobial activity at micromolar concentrations. The tails endow latartoxins with the ability to bind and damage membranes; LtTx show cytolytic activity in fly larvae neuromuscular preparations. We suggest a membrane-dependent mode of action for latartoxins with their C-terminal linear modules acting as anchoring devices.
authors.affiliation: M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russian Federation.
authors.forename: Alexey I
authors.initials: AI
authors.lastname: Kuzmenkov
authors.forename: Irina M
authors.initials: IM
authors.lastname: Fedorova
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Vassilevski
authors.forename: Eugene V
authors.initials: EV
authors.lastname: Grishin
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002942:Circular Dichroism; D003545:Cysteine / Q000737:chemistry*; D018076:DNA, Complementary / Q000378:metabolism; D004220:Disulfides / Q000737:chemistry; D004594:Electrophysiology / Q000379:methods; D007306:Insecticides / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D013058:Mass Spectrometry / Q000379:methods; D008969:Molecular Sequence Data; D009498:Neurotoxins / Q000737:chemistry; D010447:Peptide Hydrolases / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013111:Spider Venoms / Q000737:chemistry* / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000737:chemistry
chemical_list: D000596:Amino Acids; D018076:DNA, Complementary; D004220:Disulfides; D007306:Insecticides; D008055:Lipids; D009498:Neurotoxins; D010455:Peptides; D013111:Spider Venoms; D013438:Sulfhydryl Compounds; D010447:Peptide Hydrolases; D003545:Cysteine