title: A venom-derived neurotoxin, CsTx-1, from the spider Cupiennius salei exhibits cytolytic activities.
abstract: CsTx-1, the main neurotoxic acting peptide in the venom of the spider Cupiennius salei, is composed of 74 amino acid residues, exhibits an inhibitory cysteine knot motif, and is further characterized by its highly cationic charged C terminus. Venom gland cDNA library analysis predicted a prepropeptide structure for CsTx-1 precursor. In the presence of trifluoroethanol, CsTx-1 and the long C-terminal part alone (CT1-long; Gly-45-Lys-74) exhibit an α-helical structure, as determined by CD measurements. CsTx-1 and CT1-long are insecticidal toward Drosophila flies and destroys Escherichia coli SBS 363 cells. CsTx-1 causes a stable and irreversible depolarization of insect larvae muscle cells and frog neuromuscular preparations, which seem to be receptor-independent. Furthermore, this membranolytic activity could be measured for Xenopus oocytes, in which CsTx-1 and CT1-long increase ion permeability non-specifically. These results support our assumption that the membranolytic activities of CsTx-1 are caused by its C-terminal tail, CT1-long. Together, CsTx-1 exhibits two different functions; as a neurotoxin it inhibits L-type Ca(2+) channels, and as a membranolytic peptide it destroys a variety of prokaryotic and eukaryotic cell membranes. Such a dualism is discussed as an important new mechanism for the evolution of spider venomous peptides.
authors.affiliation: Institute of Ecology and Evolution, University of Bern, Baltzerstrasse 6, CH-3012 Bern, Switzerland. lucia.kuhn@iee.unibe.ch
authors.forename: Lucia
authors.initials: L
authors.lastname: Kuhn-Nentwig
authors.forename: Irina M
authors.initials: IM
authors.lastname: Fedorova
authors.forename: Benjamin P
authors.initials: BP
authors.lastname: Lüscher
authors.forename: Lukas S
authors.initials: LS
authors.lastname: Kopp
authors.forename: Christian
authors.initials: C
authors.lastname: Trachsel
authors.forename: Johann
authors.initials: J
authors.lastname: Schaller
authors.forename: Xuan Lan
authors.initials: XL
authors.lastname: Vu
authors.forename: Thomas
authors.initials: T
authors.lastname: Seebeck
authors.forename: Kathrin
authors.initials: K
authors.lastname: Streitberger
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Nentwig
authors.forename: Erwin
authors.initials: E
authors.lastname: Sigel
authors.forename: Lev G
authors.initials: LG
authors.lastname: Magazanik
mesh_terms: D000818:Animals; D020746:Calcium Channels, L-Type / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D004331:Drosophila melanogaster; D004926:Escherichia coli / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D019143:Evolution, Molecular; D005260:Female; D018482:Muscle, Skeletal / Q000737:chemistry / Q000378:metabolism; D009498:Neurotoxins / Q000737:chemistry* / Q000235:genetics; D017434:Protein Structure, Tertiary; D011896:Rana temporaria; D013111:Spider Venoms / Q000737:chemistry* / Q000235:genetics; D013112:Spiders / Q000737:chemistry* / Q000235:genetics; D014982:Xenopus laevis
chemical_list: C523732:CSTX-1, Cupiennius salei; D020746:Calcium Channels, L-Type; D018076:DNA, Complementary; D009498:Neurotoxins; D013111:Spider Venoms