HORSESHOE-CRAB COAGULOGEN IS AN INVERTEBRATE PROTEIN WITH A NERVE GROWTH FACTOR-LIKE DOMAIN

The rapid clotting of the horseshoe crab hemolymph is essential for bo th its host defense and hemostasis. It is mediated by the clotting cas cade system which consists of four serine proteinase zymogens and the clottable protein coagulogen. Coagulogen, the target protein of the ca scade, is converted to an insoluble gel upon activation of the cascade , giving rise to clot formation. Thus this cascade is reminiscent of t he mammalian blood coagulation leading to fibrin clot. The structural analysis of coagulogen revealed a polypeptide fold and disulfide bridg e pattern in the C-terminal half of the molecule very similar to nerve growth factor (NGF). This finding assigns coagulogen as the first str ucturally characterized invertebrate protein which belongs to the cyst ine knot superfamily. The putative structural similarity of coagulogen and the Drosophila morphogen Spaetzle as well as the homology of its processing proteinases suggests a common origin of the two functionall y different cascades. This would exemplify a divergent evolution of tw o proteinase cascades having totally different functions from common a ncestors in a long history of evolution.