The role of weak protein-protein interactions in multivalent lectin-carbohydrate binding: Crystal structure of cross-linked FRIL

Binding of multivalent glycoconjugates by lectins often leads to the format ion of cross-linked complexes. Type I cross-links, which are one-dimensiona l, are formed by a divalent lectin and a divalent glycoconjugate. Type II c ross-links, which are two or three-dimensional, occur when a lectin or glyc oconjugate has a Valence greater than two. Type II complexes are a source o f additional specificity, since homogeneous type II complexes are formed in the presence of mixtures of lectins and glycoconjugates. This additional s pecificity is thought to become important when a lectin interacts with clus ters of glycoconjugates, e.g. as is present on the cell surface. The crysta l structure of the Glc/Man binding legume lectin FRIL in complex with a tri saccharide provides a molecular snapshot of how weak protein-protein intera ctions, which are not observed in solution, can become important when a cro ss-linked complex is formed. In solution, FRIL is a divalent dimer, but in the crystal FRIL forms a tetramer, which allows for the formation of an int ricate type II cross-linked complex with the divalent trisaccharide. The de pendence on weak protein-protein interactions can ensure that a specific ty pe II cross-linked complex and its associated specificity can occur only un der stringent conditions, which explains why lectins are often found formin g higher-order oligomers. (C) 2000 Academic Press.