InterPro domain: IPR036574

Knottins are small proteins characterised by a cystine-knot [ 1 ]. They constitute a large family of structurally related peptides with diverse biological functions, including inhibitors, anti-microbial peptides and toxins [ 2 ]. Their structure is composed of a disulfide-bound fold and contains beta-hairpin with two adjacent disulfides.

The scorpion toxin-like domain is found in a subgroup of metazoan knottins mainly from the arthropoda, which include the antibacterial defensins [ 3 ] and the scorpion alpha-neurotoxins [ 4 , 5 ]. The plant sequences include members of the gamma-thionin family, which are plant defensins that have no antifungal activity. Other members are insect alpha-amylase inhibitors, cysteine-rich antifungal proteins and proteins annotated as proteinase inhibitors; those that are characterised belong to MEROPS inhibitor family I18, clan I.

1. KNOTTIN: the knottin or inhibitor cystine knot scaffold in 2007. Nucleic Acids Res. 36, D314-9
2. Squash inhibitors: from structural motifs to macrocyclic knottins. Curr. Protein Pept. Sci. 5, 341-349
3. Solution structure of gamma 1-H and gamma 1-P thionins from barley and wheat endosperm determined by 1H-NMR: a structural motif common to toxic arthropod proteins. Biochemistry 32, 715-24
4. Crystallization and preliminary crystallographic study of rBmKalphaIT1, a recombinant alpha-insect toxin from the scorpion Buthus martensii Karsch. Acta Crystallogr. D Biol. Crystallogr. 59, 1635-6
5. Biochemical, electrophysiological and immunological characterization of the venom from Centruroides baergi, a new scorpion species of medical importance in Mexico. Toxicon 184, 10-18