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 hos t defense molecule. Carbohydrate binding is critical to its host defense pr operties, but the precise polysaccharide structures recognized by the prote in 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)-linke d glucosyl homopolysaccharide (pustulan and laminarin, respectively), sugge sting that SP-D recognizes only certain polysaccharide configurations, like ly through differential binding to nonterminal glucosyl residues. In this s tudy we have computationally docked alpha/beta -D-glucopyranose and alpha/b eta-(1 -->2)-, alpha/beta-(1 -->3)-, alpha/beta-(1 -->4)-, and alpha/beta-( 1 -->6)-linked glucosyl trisaccharides into the SP-D carbohydrate recogniti on domain. As with the mannose-binding proteins, we found significant hydro gen bonding between the protein and the vicinal, equatorial OH groups at th e 3 and 4 positions on the sugar ring. Our docking studies predict that alp ha/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 in ternal 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 mode ling studies. Given the sequence and structural similarity between SP-D and other C-type lectins, many of the predicted interactions should be applica ble to this protein family.