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
Related in: MedlinePlus
Mentions: Langerin binding to mannans and β-glucans that are components of fungal cell walls has been documented.1 The structures described above suggest a mechanism for the binding of Manα1–2Man units in the main chains or branches of mannans. The interaction with β-glucans was probed using a complex of Glcβ1–3Glcβ1–3Glc (laminaritriose) bound to the langerin CRD. In one copy of the CRD, a single-glucose residue representing the nonreducing end of the trisaccharide is visible, with its 3-OH and 4-OH groups coordinating Ca2+ and forming hydrogen bonds with Ca2+ ligands, as previously seen for the reducing glucose residue in maltose (Glcβ1–4Glc)9 (Fig. 4a and b). However, no additional interactions with the other two sugar residues are observed. In β1–6-linked glucans, there would be multiple residues that could bind in this mode, although only the nonreducing termini of β1–3 glucans would be able to bind. In another copy, a Glcβ1–3Glc disaccharide is visible, with the reducing end of the trisaccharide binding to Ca2+ through the equatorial 1-OH and 2-OH groups (Fig. 4c and d), indicating that langerin could bind to either end of a free glucan. The observed β1–3 linkage falls in the broad conformational minimum observed in databases of glycan structures.13
Affiliation: Department of Structural Biology, Stanford University School of Medicine, Stanford, CA, USA.