The 2.0-angstrom crystal structure of tachylectin 5A provides evidence forthe common origin of the innate immunity and the blood coagulation systems

Because invertebrates lack an adaptive immune system, they had to evolve ef fective intrinsic defense strategies against a variety of microbial pathoge ns. This ancient form of host defense, the innate immunity, is present in a ll multicellular organisms including humans. The innate immune system of th e Japanese horseshoe crab Tachypleus tridentatus, serving as a model organi sm, includes a hemolymph coagulation system, which participates both in def ense against microbes and in hemostasis. Early work on the evolution of ver tebrate fibrinogen suggested a common origin of the arthropod hemolymph coa gulation and the vertebrate blood coagulation systems. However, this conjec ture could not be verified by comparing the structures of coagulogen, the c lotting protein of the horseshoe crab, and of mammalian fibrinogen. Here we report the crystal structure of tachylectin 5A (TL5A), a nonself-recognizi ng lectin from the hemolymph plasma of T. tridentatus. TL5A shares not only a common fold but also related functional sites with the gamma fragment of mammalian fibrinogen. Our observations provide the first structural eviden ce of a common ancestor for the innate immunity and the blood coagulation s ystems.