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. Despite their different biological functions the following peptides appear to have evolved from the same ancestors and belong to the huwentoxin-1 family [1]:

• Ornithoctonus huwena (Chinese bird spider) (Selenocosmia huwena) huwentoxin-I (HWTX-I), a 33 amino acid peptide, which can block the N-type high-voltage activated calcium channels [2].
• Ornithoctonus huwena (Chinese bird spider) (Selenocosmia huwena) huwentoxin-IIIa (HWTX-IIIa).
• Ornithoctonus huwena (Chinese bird spider) (Selenocosmia huwena) huwentoxin-IV (HWTX-IV), a 35 amino acid peptide, which is an inhibitor of tetrodotoxin (TTX) sensitive voltage-gated sodium channel [3].
• Ornithoctonus huwena (Chinese bird spider) (Selenocosmia huwena) huwentoxin-V (HWTX-V), a 35 amino acid insecticidal toxin which can reversibly paralyze in insects [4].
• Ornithoctonus huwena (Chinese bird spider) (Selenocosmia huwena) huwenlectin-I (SHL-I), a 32 amino acid peptide with haemagglutination activity but almost no neurotoxin activity.
• Selenocosmia hainana Hainantoxin-I (HNTX-I), Hainantoxin-III (HNTX-III), Hainantoxin-IV (HNTX-IV) and Hainantoxin-V (HNTX-V) [5].
• Brachypelma smithii (Mexican red knee tarantula) Venom protein 5.
• Grammostola spatulata (Chilean rose tarantula) voltage sensor toxin 1.

Peptides of the huwentoxin type I family contain 6 cysteine residues involved in three disulfide bonds. The three disulfide bridges have been assigned as C1-C4, C2-C5 and C3-C6. HWTX-I adopts a compact structure consisting of a small triple-stranded antiparallel β-sheet and five β-turns (see <PDB:1QK6>) [6].

We developed a pattern for huwentoxin-1 family proteins, which have a [C-C-CC-C-C] cysteine arrangement. The three-dimensional structure of huwentoxin-1 family proteins possess a knottin scafold (see <PDOC60004>) [E1].