PROSITE documentation PDOC60022

Huwentoxin-2 family signature

The spider venoms often contain many active peptides such as neurotoxins, lectins, inhibitors to enzyme, etc. These peptides are very important for spider's hunting and defending. During the long history of spider evolution, the peptides evolved into different structures and functions. The following peptides share high similarity and belong to the huwentoxin-2 family [1,2,3,4]:

• Ornithoctonus huwena (Chinese bird spider) (Selenocosmia huwena) huwentoxin-II (HWTX-II) and huwentoxin-IIa (HWTX-IIa), which can cause reversatile paralysis in insects and are insecticidal toxins.
• Ornithoctonus huwena (Chinese bird spider) (Selenocosmia huwena) huwentoxin-VII (HWTX-VII) and huwentoxin-VIII (HWTX-VIII), which block neuromuscular transmission.
• Ornithoctonus huwena (Chinese bird spider) (Selenocosmia huwena) huwentoxin-VI (HWTX-VI).
• Brachypelma smithii (Mexican red knee tarantula) venom protein 1.
• Lasiodora parahybana (Salmon pink birdeater) lasiotoxin 1 and 2, which are toxic to mice, but not insects.
• Eurypelma californica (American tarantula) ESTX1 and ESTX2 neurotoxins.

Peptides of the huwentoxin-2 family contain 6 cysteine residues involved in three disulfide bonds. The three disulfid bridges of HWTX-II have been assigned as C1-C3, C2-C5 and C4-C6 [3]. The structure of HWTX-II contains two β-turns and a double stranded antiparallel β-sheet cross-linked by two disulfide bonds (2-5 and 4-6) (see <PDB:1I25>). Due to its unique 1-3,2-5,4-6 disulfide bond-pairing, HTWX-II does not form a cystine-knot like other spider toxins [4].

We developed a pattern for huwentoxin-2 family proteins, which contains the six conserved cysteines.