Polysaccharide Recognition by Surfactant Protein D:  Novel Interactions of a C-Type Lectin with Nonterminal Glucosyl Residues

Abstract

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 toAspergillus fumigatus is strongly inhibited by a soluble β-(1→6)-linked but not by a soluble β-(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 α/β-dglucopyranose and α/β-(1→2)-, α/β-(1→3)-, α/β-(1→4)-, and α/β-(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 α/β-(1→2)-, α-(1→4)-, and α/β-(1→6)-linked but not α/β-(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. Disciplines Biochemical and Biomolecular Engineering | Biological Engineering | Chemical Engineering CommentsThis work was supported by grants from NIH (HL-29891) and EPA (R825702 ABSTRACT: 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 -(1f6)-linked but not by a soluble -(1f3)-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 R/ -D-glucopyranose and R/ -(1f2)-, R/ -(1f3)-, R/ -(1f4)-, and R/ -(1f6)-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 R/ -(1f2)-, R-(1f4)-, and R/ -(1f6)-linked but not R/ -(1f3)-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 homopo...

Ligand Specificity of Human Surfactant Protein D

“…and Arg 343 (the first residue of the C-terminal motif) in interactions of hSP-D with the terminal glucosyl residues of a glucosyl-trisaccharide (42). The importance of Arg 343 in glucose recognition and in sterically limiting interactions with GlcNAc was confirmed in a recent mutagenesis study (43).…”

Aggregation ofCryptococcus neoformansby Surfactant Protein D Is Inhibited by Its Capsular Component Glucuronoxylomannan

“…In general, it is thought that SP-D attachment to (microbial) glycoconjugates cannot be predicted solely by analyzing their monosaccharide compositions, as the manner in which the separate saccharides are assembled within these structures seems to be very important (1). The carbohydrate moieties of both MPs have very similar monosaccharide compositions, containing high percentages of residues for which SP-D has high affinity when these residues are presented as monosaccharides (42).…”

Surfactant Protein D Binds Selectively toKlebsiella pneumoniaeLipopolysaccharides Containing Mannose-Rich O-Antigens

“…If the interactions of SP-D with the O3 or O5 Ags are weak, it is possible that they are stabilized by residual interactions with the core oligosaccharide, even though the latter interactions are too weak to mediate SP-D binding in the presence of a nonreactive O-Ag. In this regard, recent computer docking studies suggest that SP-D can favorably interact with internal-as well as terminal-glucose residues (45). Thus, the presence of O-Ag should not preclude interactions of SP-D with glucose (or heptose) residues in the subjacent core oligosaccharide.…”