Isolation of a funnel-web spider polypeptide with homology to mamba intestinal toxin 1 and the embryonic head inducer Dickkopf-1.
We have isolated and determined the amino acid sequence of a novel peptide component from the venom of the Australian funnel-web spider Hadronyche versuta. This 68-residue toxin, ACTX-Hvf17, does not function like classical neurotoxins in modulating ion channel function as evidenced by its lack of insecticidal activity and its inability to affect vertebrate smooth or skeletal muscle contractility. The peptide shows significant sequence homology with mamba intestinal toxin 1 (MIT1) and to a lesser extent with a variety of colipases. The strong structural homology between MIT1 and porcine colipase leads us to propose that ACTX-Hvf17 also adopts the MIT1/colipase three-dimensional fold. However, we show that ACTX-Hvf17 has no colipase activity and does not stimulate muscle contractility like MITI. We also show that MIT1 and ACTX-Hvf17 display significant sequence homology with the C-terminal cysteine-rich domain of the Dickkopf-1 family of proteins that induce head formation in developing embryos, which leads us to propose that this domain of Dickkopf-1 also adopts the MIT1 colipase fold.
Szeto
T H
TH
Department of Biochemistry, University of Connecticut Health Center, Farmington 06032, USA.
Wang
X H
XH
Smith
R
R
Connor
M
M
Christie
M J
MJ
Nicholson
G M
GM
King
G F
GF
D000595:Amino Acid Sequence; D000818:Animals; D002645:Chickens; D002851:Chromatography, High Pressure Liquid; D003545:Cysteine / Q000032:analysis; D004220:Disulfides / Q000032:analysis; D005260:Female; D005612:Freeze Drying; D006135:Gryllidae; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation; D010084:Oxidation-Reduction; D010455:Peptides / Q000737:chemistry* / Q000302:isolation & purification / Q000633:toxicity; D011506:Proteins / Q000737:chemistry* / Q000302:isolation & purification; D051381:Rats; D017386:Sequence Homology, Amino Acid; D013111:Spider Venoms / Q000737:chemistry* / Q000302:isolation & purification; D013112:Spiders / Q000378:metabolism*; D014649:Vas Deferens / Q000187:drug effects / Q000294:innervation; D014688:Venoms / Q000737:chemistry* / Q000302:isolation & purification
D004220:Disulfides; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D011506:Proteins; D013111:Spider Venoms; D014688:Venoms; C402142:mamba intestinal toxin 1; D003545:Cysteine