title: The role of weak protein-protein interactions in multivalent lectin-carbohydrate binding: crystal structure of cross-linked FRIL.
abstract: 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.
authors.affiliation: Laboratorium voor Ultrastructuur, Vlaams Interuniversitair Instituut voor Biotechnologie, Vrije Universiteit Brussel, Paardenstraat 65, Sint-Genesius-Rode, B-1640, Belgium. thamelry@vub.ac.be
authors.forename: T W
authors.initials: TW
authors.lastname: Hamelryck
authors.forename: J G
authors.initials: JG
authors.lastname: Moore
authors.forename: M J
authors.initials: MJ
authors.lastname: Chrispeels
authors.forename: R
authors.initials: R
authors.lastname: Loris
authors.forename: L
authors.initials: L
authors.lastname: Wyns
mesh_terms: D001665:Binding Sites; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D003208:Concanavalin A / Q000737:chemistry / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000737:chemistry / Q000378:metabolism*; D018360:Crystallography, X-Ray; D019281:Dimerization; D007887:Fabaceae / Q000737:chemistry*; D006860:Hydrogen Bonding; D037102:Lectins / Q000737:chemistry* / Q000378:metabolism*; D008358:Mannose / Q000737:chemistry / Q000378:metabolism; D037241:Mannose-Binding Lectins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D037121:Plant Lectins; D010946:Plants, Medicinal; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D013379:Substrate Specificity; D014312:Trisaccharides / Q000737:chemistry / Q000378:metabolism*
chemical_list: D003432:Cross-Linking Reagents; C117675:FRIL protein, Dolichos lablab; D037102:Lectins; D037241:Mannose-Binding Lectins; D037121:Plant Lectins; D014312:Trisaccharides; D003208:Concanavalin A; D008358:Mannose