Document Type

Article

Publication Date

7-1-2001

Journal or Book Title

Biochemistry

Volume

40

First Page

7789

Last Page

7798

DOI

10.1021/bi002901q

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-d-glucopyranose 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.

Comments

This work was supported by grants from NIH (HL-29891) and EPA (R825702). M.J.A. was funded by Great West Life Assurance and Andrew Goodman Fellowships at the National Jewish Medical and Research Center, and A.L. was supported by National Science Foundation IGERT Program Award 9972653.

Posted with permission from Biochemistry, 40 (2001): 7789–7798, doi:10.1021/bi002901q. Copyright 2001 American Chemical Society.

Copyright Owner

American Chemical Society

Language

en

File Format

application/pdf

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