Structural basis for langerin recognition of diverse pathogen and mammalian glycans through a single binding site.
Bottom Line: The fucose moiety of the blood group B trisaccharide Galα1-3(Fucα1-2)Gal also binds to the Ca(2+) site, and selective binding to this glycan compared to other fucose-containing oligosaccharides results from additional favorable interactions of the nonreducing terminal galactose, as well as of the fucose residue.Surprisingly, the equatorial 3-OH group and the axial 4-OH group of the galactose residue in 6SO(4)-Galβ1-4GlcNAc also coordinate Ca(2+), a heretofore unobserved mode of galactose binding in a C-type carbohydrate-recognition domain bearing the Glu-Pro-Asn signature motif characteristic of mannose binding sites.Salt bridges between the sulfate group and two lysine residues appear to compensate for the nonoptimal binding of galactose at this site.
Affiliation: Department of Structural Biology, Stanford University School of Medicine, Stanford, CA, USA.Show MeSH
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Mentions: Electron density in all four copies of the CRD clearly shows both 6SO4–Gal and GlcNAc residues (Fig. 5a and b). In spite of the fact that langerin binds poorly to galactose compared to mannose and fucose,6 the galactose residue is bound in the Ca2+ site (Fig. 5a and c). The Ca2+ ligands Glu293 and Asn307 form hydrogen bonds with the axial 4-OH group of 6SO4–Gal, and Glu285 and Asn287 coordinate Ca2+ and form hydrogen bonds with the equatorial 3-OH group of 6SO4–Gal. The equatorial/axial geometry of these two hydroxyl groups tilts the galactose pyranose ring relative to mannose (Fig. 5d and e) so that it packs against Ala289. The SO4 group forms salt bridges with Lys299 and Lys313, consistent with previously published results showing that Lys299Ala or Lys313Ala mutations abolish binding to the disaccharide2 (Fig. 5f). The charge–charge interactions between these lysine residues and the sulfate group must compensate for the presumably nonoptimal Ca2+ ligation of galactose at a site with an EPN signature because langerin does not bind to nonsulfated galactosides.2,6
Affiliation: Department of Structural Biology, Stanford University School of Medicine, Stanford, CA, USA.