Polysaccharide recognition by surfactant protein D: novel interactions of a C-type lectin with nonterminal glucosyl residues.

Surfactant protein D (SP-D), a C-type lectin, is an important pulmonary host defense molecule. Carbohydrate binding is critical to its host defense properties, but the precise polysaccharide structures recognized by the protein are unknown. SP-D binding to Aspergillus fumigatus is strongly inhibited by a soluble beta-(1-->6)-linked but not by a soluble beta-(1-->3)-linked glucosyl homopolysaccharide (pustulan and laminarin, respectively), suggesting that SP-D recognizes only certain polysaccharide configurations, likely through differential binding to nonterminal glucosyl residues. In this study we have computationally docked alpha/beta-D-glucopyranose and alpha/beta-(1-->2)-, alpha/beta-(1-->3)-, alpha/beta-(1-->4)-, and alpha/beta-(1-->6)-linked glucosyl trisaccharides into the SP-D carbohydrate recognition domain. As with the mannose-binding proteins, we found significant hydrogen bonding between the protein and the vicinal, equatorial OH groups at the 3 and 4 positions on the sugar ring. Our docking studies predict that alpha/beta-(1-->2)-, alpha-(1-->4)-, and alpha/beta-(1-->6)-linked but not alpha/beta-(1-->3)-linked glucosyl trisaccharides can be bound by their internal glucosyl residues and that binding also occurs through interactions of the protein with the 2- and 3-equatorial OH groups on the glucosyl ring. By using various soluble glucosyl homopolysaccharides as inhibitors of SP-D carbohydrate binding, we confirmed the interactions predicted by our modeling studies. Given the sequence and structural similarity between SP-D and other C-type lectins, many of the predicted interactions should be applicable to this protein family.