The structure of spider toxin huwentoxin-II with unique disulfide linkage: evidence for structural evolution.
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.
Shu
Qin
Q
Life Science College, Peking University, Beijing 100871, People's Republic of China.
Lu
Shan-Yun
SY
Gu
Xiao-Cheng
XC
Liang
Song-Ping
SP
D000595:Amino Acid Sequence; D000818:Animals; D004220:Disulfides / Q000737:chemistry*; D019143:Evolution, Molecular; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009498:Neurotoxins / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding; D017386:Sequence Homology, Amino Acid; D013111:Spider Venoms / Q000737:chemistry*; D013112:Spiders / Q000737:chemistry*
D004220:Disulfides; D009498:Neurotoxins; D013111:Spider Venoms; C121745:huwentoxin II