STRUCTURES OF A LEGUME LECTIN COMPLEXED WITH THE HUMAN LACTOTRANSFERRIN N2 FRAGMENT, AND WITH AN ISOLATED BIANTENNARY GLYCOPEPTIDE - ROLE OF THE FUCOSE MOIETY

Background: Lectins mediate cell-cell interactions by specifically rec ognizing oligosaccharide chains. Legume lectins serve as mediators for the symbiotic interactions between plants and nitrogen-fixing microor ganisms, an important process in the nitrogen cycle. Lectins from the Viciae tribe have a high affinity for the fucosylated biantennary N-ac etyllactosamine-type glycans which are to be found in the majority of N-glycosylproteins. While the structures of several lectins complexed with incomplete oligosaccharides have been solved, no previous structu re has included the complete glycoprotein. Results: We have determined the crystal structures of Lathyrus ochrus isolectin II complexed with the N2 monoglycosylated fragment of human lactotransferrin (18 kDa) a nd an isolated glycopeptide (2.1 kDa) fragment of human lactotransferr in (at 3.3 angstrom and 2.8 angstrom resolution, respectively). Compar ison between the two structures showed that the protein part of the gl ycoprotein has little influence on either the stabilization of the com plex or the sugar conformation. In both cases the oligosaccharide adop ts the same extended conformation. Besides the essential mannose moiet y of the monosaccharide-binding site, the fucose-1' of the core has a large surface of interaction with the lectin. This oligosaccharide con formation differs substantially from that seen in the previously deter mined isolectin I-octasaccharide complex. Comparison of our structure with that of concanavalin A (ConA) suggests that the ConA binding site cannot accommodate this fucose. Conclusions: Our results explain the observation that Viciae lectins have a higher affinity for fucosylated oligosaccharides than for unfucosylated ones, whereas the affinity of ConA for these types of oligosaccharides is similar. This explanation is testable by mutagenesis experiments. Our structure shows a large c omplementary surface area between the oligosaccharide and the lectin, in contrast with the recently determined structure of a complex betwee n the carbohydrate recognition domain of a C-type mammalian lectin and an oligomannoside, where only the non-reducing terminal mannose resid ue interacts with the lectin.