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.
Allen
M J
MJ
Department of Medicine, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, Colorado 80206-2761, USA. allenm@njc.org
Laederach
A
A
Reilly
P J
PJ
Mason
R J
RJ
D001232:Aspergillus fumigatus / Q000378:metabolism; D001667:Binding, Competitive; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002266:Carboxymethylcellulose Sodium / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006023:Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D037102:Lectins / Q000378:metabolism*; D037181:Lectins, C-Type; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011134:Polysaccharides / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D037663:Pulmonary Surfactant-Associated Protein D; D011663:Pulmonary Surfactants / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D013172:Spores, Fungal / Q000378:metabolism; D014312:Trisaccharides / Q000378:metabolism
D006023:Glycoproteins; D037102:Lectins; D037181:Lectins, C-Type; D011134:Polysaccharides; D037663:Pulmonary Surfactant-Associated Protein D; D011663:Pulmonary Surfactants; D011994:Recombinant Proteins; D014312:Trisaccharides; D005947:Glucose; D002266:Carboxymethylcellulose Sodium