Research Project
Full description Venoms are mixtures of bioactive compounds called toxins. Despite their molecular diversity, most toxins can be classified into just a few three-dimensional (3D) folds. Host defence peptides (defensins) with a cystine-stabilised α/β fold (CSαβ) are one such group. CSαβ peptides represent one of the most widespread peptide superfamilies known, and have evolved as toxins on multiple occasions. Here we describe the 3D structure of a centipede venom peptide that defines a new type of CSαβ, termed the two-disulfide CSαβ fold (2ds-CSαβ). The 2ds-CSαβ contains only two internal disulfide bonds, as opposed to at least three in all other confirmed CSαβ peptides, and we show that these two forms diverged prior to the division of prokaryotes and eukaryotes. The CSαβ superfamily is thus the first peptide fold to join an exclusive group of ancient protein superfamilies thought to have originated close to the emergence of cellular life, and possibly one of the first evolutionary innovations within cellular biochemical defence.