Getting knotted: a model for the structure and activation of Spätzle

Sequence analyses show that Spätzle, the Drosophila melanogaster Toll-receptor ligand, shows striking similarity to nerve growth factor and coagulogen. Comparative modelling suggests that Spätzle adopts a cystine-knot fold and forms a dimer that contains a single, intermolecular disulphide bridge. Proteolytically cleaved Spätzle could therefore dimerize and activate the Toll receptor by inducing receptor dimerization.