The structure of spider toxin huwentoxin-II with unique disulfide linkage: evidence for structural evolution

Protein Sci. 2002 Feb;11(2):245-52. doi: 10.1110/ps.30502.

Abstract

The three-dimensional structure of huwentoxin-II (HWTX-II), an insecticidal peptide purified from the venom of spider Selenocosmia huwena with a unique disulfide bond linkage as I-III, II-V, and IV-VI, has been determined using 2D (1)H-NMR. The resulting structure of HWTX-II contains two beta-turns (C4-S7 and K24-W27) and a double-stranded antiparallel beta-sheet (W27-C29 and C34-K36). Although the C-terminal double-stranded beta-sheet cross-linked by two disulfide bonds (II-V and IV-VI in HWTX-II, II-V and III-VI in the ICK molecules) is conserved both in HWTX-II and the ICK molecules, the structure of HWTX-II is unexpected absence of the cystine knot because of its unique disulfide linkage. It suggests that HWTX-II adopts a novel scaffold different from the ICK motif that is adopted by all other spider toxin structures elucidated thus far. Furthermore, the structure of HWTX-II, which conforms to the disulfide-directed beta-hairpin (DDH) motif, not only supports the hypothesis that the ICK is a minor elaboration of the more ancestral DDH motif but also suggests that HWTX-II may have evolved from the same structural ancestor.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Disulfides / chemistry*
  • Evolution, Molecular
  • Magnetic Resonance Spectroscopy / methods*
  • Models, Molecular
  • Molecular Sequence Data
  • Neurotoxins / chemistry*
  • Protein Conformation
  • Protein Folding
  • Sequence Homology, Amino Acid
  • Spider Venoms / chemistry*
  • Spiders / chemistry*

Substances

  • Disulfides
  • Neurotoxins
  • Spider Venoms
  • huwentoxin II

Associated data

  • PDB/1AZ6
  • PDB/1DL0
  • PDB/1OAV
  • PDB/1QK6
  • PDB/1VTX