Crystal structure of the jacalin-T-antigen complex and a comparative study of lectin-T-antigen complexes

Thomsen–Friedenreich antigen (Galb1–3GalNAc), generally known as T-antigen, is expressed in more than 85 % of human carcinomas. Therefore, proteins which specifically bind T-antigen have potential diagnostic value. Jacalin, a lectin from jack fruit (Artocarpus integrifolia) seeds, is a tetramer of molecular mass 66 kDa. It is one of the very few proteins which are known to bind T-antigen. The crystal structure of the jacalin–T-antigen complex has been determined at 1.62 A ̊ resolution. The interactions of the disaccharide at the binding site are predominantly through the GalNAc moiety, with Gal interacting only through water molecules. They include a hydrogen bond between the anomeric oxygen of GalNAc and the p electrons of an aromatic side-chain. Several intermolecular inter-actions involving the bound carbohydrate contribute to the stability of the crystal structure. The present structure, along with that of the Me-a-Gal complex, provides a reasonable qualitative explanation for the known affinities of jacalin to different carbohydrate ligands and a plausible model of the binding of the lectin to T-antigen O-linked to seryl or threonyl residues. Including the present one, the structures of five lectin–T-antigen complexes are available. GalNAc occupies the primary binding site in three of them, while Gal occupies the site in two. The choice appears to be related to the ability of the lectin to bind sialylated sugars. In either case, most of the lectin–disaccharide interactions are at the primary binding site. The conformation of T-antigen in the five complexes is nearly the same