title: Role of the structurally disordered N- and C-terminal residues in the Janus-faced atracotoxins.
abstract: The Janus-faced atracotoxins (J-ACTXs) are a family of insect-specific excitatory toxins isolated from the venom of Australian funnel-web spiders (genera Atrax and Hadronyche). In addition to a classical cystine knot motif, these toxins contain a rare vicinal disulfide bond. While the vicinal disulfide is known to be critical for insecticidal activity, the role of other residues in toxin function remains to be determined. In this study, we probed the role of the structurally disordered N- and C-terminal residues using a panel of recombinant mutants of the prototypic family member J-ACTX-Hv1c. We found that the structurally disordered C-terminal residues (Glu 36 and Pro 37) were dispensable for toxin function. However, whereas deletion of Ala 1 had minimal impact on toxin function, deletion of both Ala 1 and Ile 2 decreased insecticidal activity more than 70-fold. We propose that Ile 2 forms a part of the target binding site of J-ACTX-Hv1c.
authors.affiliation: Department of Biochemistry, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06032, USA.
authors.forename: Francesco
authors.initials: F
authors.lastname: Maggio
authors.forename: Glenn F
authors.initials: GF
authors.lastname: King
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006793:Houseflies; D007300:Insect Control / Q000379:methods; D007306:Insecticides; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D015202:Protein Engineering; D011994:Recombinant Proteins / Q000235:genetics; D013111:Spider Venoms / Q000737:chemistry / Q000235:genetics*; D013112:Spiders; D013329:Structure-Activity Relationship
chemical_list: D007306:Insecticides; D011994:Recombinant Proteins; D013111:Spider Venoms; C406870:delta-atracotoxin-HV1