Horseshoe crab acetyl group-recognizing lectins involved in innate immunity are structurally related to fibrinogen

We have characterized and cloned newly isolated lectins front hemolymph pla sma of the horseshoe crab Tachypleus tridentatus, which we named tachylecti ns 5A and 5B (TLs-5), TLs-5 agglutinated all types of human erythrocytes an d Gram-positive and Gram-negative bacteria. TLs-5 specifically recognize ac etyl group-containing substances including noncarbohydrates; the acetyl gro up is required and is sufficient for recognition. TLs-5 enhanced the antimi crobial activity of a horseshoe crab-derived big defensin. cDNA sequences o f TLs-5 indicated that they consist of a short N-terminal Cys-containing se gment and a C-terminal fibrinogen-like domain with the highest sequence ide ntity (51%) to that of mammalian ficolins. TLs-5, however, lack the collage nous domain found in a kind of "bouquet arrangement" of ficolins and collec tins. Electron microscopy revealed that TLs-5 form two- to four-bladed prop eller structures. The horseshoe crab is equipped with a unique functional h omologue of vertebrate fibrinogen, coagulogen, as the target protein of the clotting cascade. Our observations clearly show that the horseshoe crab ha s fibrinogen-related molecules in hemolymph plasma and that they function a s nonself-recognizing lectins, An ancestor of fibrinogen may have functione d as a nonself-recognizing protein.