Isolation of a funnel-web spider polypeptide with homology to mamba intestinal toxin 1 and the embryonic head inducer Dickkopf-1

Tim H. Szeto, Xiu Hong Wang, Ross Smith, Mark Connor, MacDonald J. Christie, Graham M. Nicholson, Glenn F. King*

*Corresponding author for this work

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

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 MIT1. 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. Copyright (C) 1999 Elsevier Science Ltd.

Original languageEnglish
Pages (from-to)429-442
Number of pages14
JournalToxicon
Volume38
Issue number3
DOIs
Publication statusPublished - Mar 2000
Externally publishedYes

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