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: The bound blood group B trisaccharide was found to have the same orientation in all four CRDs in the asymmetric unit of the cocrystals. The fucose moiety binds to the Ca2+ site, with the equatorial 2-OH and 3-OH groups coordinating Ca2+ (Fig. 3a–c). In addition to the four Ca2+ ligands that form hydrogen bonds to the 2-OH and 3-OH groups of fucose, the 4-OH group forms a hydrogen bond with Lys299, and the ring 3-C packs against the side chain of Ala289 (Fig. 3c and d). The central galactose residue is positioned away from the protein, but the nonreducing galactose residue packs against Cα of Gly284 and the side chains of Ile282, Glu285, and Asn287. The 4-OH group of this galactose also forms a hydrogen bond with the backbone carbonyl oxygen of Pro283, and the 6-OH group is hydrogen bonded to the side-chain amide group of Asn287 (Fig. 3e and f). Since Asn287 also donates a hydrogen bond to the bound fucose, this residue bridges the fucose and galactose moieties (Fig. 3c and e). The 2-OH group of the nonreducing terminal galactose points away from the protein surface, explaining why the blood group A trisaccharide GalNAcα1–3(Fucα1–2)Gal can bind to langerin, albeit more weakly than the blood group B trisaccharide.
Affiliation: Department of Structural Biology, Stanford University School of Medicine, Stanford, CA, USA.