Tachylectin-2: crystal structure of a specific GlcNAc/GalNAc-binding lectin involved in the innate immunity host defense of the Japanese horseshoe crab Tachypleus tridentatus

Tachylectin-2, isolated from large granules of the hemocytes of the Japanes e horseshoe crab (Tachypleus tridentatus), is a 236 amino acid protein belo nging to the lectins. It binds specifically to N-acetylglucosamine and N-ac etylgalactosamine and is a part of the innate immunity host defense system of the horseshoe crab. The X-ray structure of tachylectin-2 was solved at 2 .0 Angstrom resolution by the multiple isomorphous replacement method and t his molecular model was employed to solve the X-ray structure of the comple x with N-acetylglucosamine. Tachylectin-2 is the first protein displaying a five-bladed beta-propeller structure. Five four-stranded antiparallel beta -sheets of W-like topology are arranged around a central water-filled tunne l, with the water molecules arranged as a pentagonal dodecahedron. Tachylec tin-2 exhibits five virtually identical binding sites, one in each beta-she et, The binding sites are located between adjacent beta-sheets and are made by a large loop between the outermost strands of the beta-sheets and the c onnecting segment from the previous beta-sheet, The high number of five bin ding sites within the single polypeptide chain strongly suggests the recogn ition of carbohydrate surface structures of pathogens with a fairly high li gand density. Thus, tachylectin-2 employs strict specificity for certain N- acetyl sugars as well as the surface ligand density for self/non-self recog nition.