Discovery and characterization of a family of insecticidal neurotoxins with a rare vicinal disulfide bridge.
We have isolated a family of insect-selective neurotoxins from the venom of the Australian funnel-web spider that appear to be good candidates for biopesticide engineering. These peptides, which we have named the Janus-faced atracotoxins (J-ACTXs), each contain 36 or 37 residues, with four disulfide bridges, and they show no homology to any sequences in the protein/DNA databases. The three-dimensional structure of one of these toxins reveals an extremely rare vicinal disulfide bridge that we demonstrate to be critical for insecticidal activity. We propose that J-ACTX comprises an ancestral protein fold that we refer to as the disulfide-directed beta-hairpin.
Wang
X
X
Department of Biochemistry, University of Connecticut Health Center, Farmington 06032, USA.
Connor
M
M
Smith
R
R
Maciejewski
M W
MW
Howden
M E
ME
Nicholson
G M
GM
Christie
M J
MJ
King
G F
GF
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002851:Chromatography, High Pressure Liquid; D004220:Disulfides / Q000737:chemistry* / Q000378:metabolism*; D019143:Evolution, Molecular; D007313:Insecta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007306:Insecticides / Q000737:chemistry* / Q000302:isolation & purification* / Q000633:toxicity; D007928:Lethal Dose 50; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009498:Neurotoxins / Q000737:chemistry* / Q000302:isolation & purification* / Q000633:toxicity; D019906:Nuclear Magnetic Resonance, Biomolecular; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011950:Receptors, Cholinergic / Q000378:metabolism; D016415:Sequence Alignment; D013045:Species Specificity; D013111:Spider Venoms / Q000737:chemistry
D004220:Disulfides; D007306:Insecticides; D009498:Neurotoxins; D011950:Receptors, Cholinergic; D013111:Spider Venoms