UniProt release 11.3

Knottins or how to knit in the protein world

Knottins (also called inhibitor cystine knots or ICKs) are small disulfide-rich proteins characterized by a special "disulfide through disulfide knot". This knot is obtained when one disulfide bridge crosses the macrocycle formed by two other disulfides and the interconnecting backbone (disulfide 3-6 goes through disulfides 1-4 and 2-5).

The knottin structure is found in many unrelated families, such as plant protease inhibitors, cyclotides, toxins from cone snails, spiders, insects, horseshoe crabs and scorpions, gurmarin-like peptides, agouti-related proteins, and antimicrobial peptides.

In collaboration with Laurent Chiche (CNRS, Montpellier), about 450 UniProtKB/Swiss-Prot entries have been updated with knottin structural information. They can be retrieved with the newly introduced keyword Knottin.

Examples:

• Agouti-signaling protein precursor (P42127)
• Trypsin inhibitor 3 (P83394)
• Hanatoxin-1 (P56852)