CRYSTAL-STRUCTURE OF COAGULOGEN, THE CLOTTING PROTEIN FROM HORSESHOE-CRAB - A STRUCTURAL HOMOLOG OF NERVE GROWTH-FACTOR

The clotting cascade system of the horseshoe crab (Limulus) is involve d in both haemostasis and host defence, The cascade results in the con version of coagulogen, a soluble protein, into an insoluble coagulin g el, The clotting enzyme excises the fragment peptide C from coagulogen , giving rise to aggregation of the monomers, The crystal structure of coagulogen reveals an elongated molecule that embraces the helical pe ptide C fragment, Cleavage and removal of the peptide C would expose a n extended hydrophobic cove, which could interact with the hydrophobic edge of a second molecule, leading to a polymeric fibre. The C-termin al half of the coagulogen molecule exhibits a striking topological sim ilarity to the neurotrophin nerve growth factor (NGF), providing the f irst evidence for a neurotrophin fold in invertebrates, Similarities b etween coagulogen and Spatzle, the Drosophila ligand of the receptor T oll, suggest that the neurotrophin fold might be considered more ancie nt and widespread than previously realized.