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

• Published in: Journal of molecular biology 2000-06, Vol.299 (4), p.875-883
• Main Authors: Hamelryck, T W, Moore, J G, Chrispeels, M J, Loris, R, Wyns, L
• Format: Article
• Language: English
• Subjects: Binding Sites; Carbohydrate Conformation; Carbohydrate Sequence; Concanavalin A - chemistry; Concanavalin A - metabolism; Cross-Linking Reagents - chemistry; Cross-Linking Reagents - metabolism; Crystallography, X-Ray; Dimerization; Fabaceae - chemistry; Hydrogen Bonding; Lectins - chemistry; Lectins - metabolism; Mannose - chemistry; Mannose - metabolism; Mannose-Binding Lectins; Models, Molecular; Molecular Sequence Data; Plant Lectins; Plants, Medicinal; Protein Binding; Protein Structure, Quaternary; Protein Structure, Secondary; Substrate Specificity; Trisaccharides - chemistry; Trisaccharides - metabolism
• ISSN: 0022-2836
• DOI: 10.1006/jmbi.2000.3785

Binding of multivalent glycoconjugates by lectins often leads to the formation of cross-linked complexes. Type I cross-links, which are one-dimensional, are formed by a divalent lectin and a divalent glycoconjugate. Type II cross-links, which are two or three-dimensional, occur when a lectin or glycoconjugate has a valence greater than two. Type II complexes are a source of additional specificity, since homogeneous type II complexes are formed in the presence of mixtures of lectins and glycoconjugates. This additional specificity is thought to become important when a lectin interacts with clusters of glycoconjugates, e.g. as is present on the cell surface. The cryst1al structure of the Glc/Man binding legume lectin FRIL in complex with a trisaccharide provides a molecular snapshot of how weak protein-protein interactions, which are not observed in solution, can become important when a cross-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 intricate type II cross-linked complex with the divalent trisaccharide. The dependence on weak protein-protein interactions can ensure that a specific type II cross-linked complex and its associated specificity can occur only under stringent conditions, which explains why lectins are often found forming higher-order oligomers.