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Structural basis for langerin recognition of diverse pathogen and mammalian glycans through a single binding site.

Feinberg H, Taylor ME, Razi N, McBride R, Knirel YA, Graham SA, Drickamer K, Weis WI - J. Mol. Biol. (2010)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Structural Biology, Stanford University School of Medicine, Stanford, CA, USA.

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Structure of the CRD of langerin bound to laminaritriose. The color scheme is the same as that described in Fig. 2. (a) Nonreducing glucose residue bound to monomer C. (b) Fo − Fc electron density map (green), calculated by omitting the sugars (3.0σ) showing laminaritriose monomer C. (c) The reducing and central glucose residues visible in monomer B. (d) Fo − Fc electron density omit maps of langerin CRD bound to laminaritriose monomer B. Map contours at 3.0σ and 2.2σ are shown in blue and green, respectively.
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f0020: Structure of the CRD of langerin bound to laminaritriose. The color scheme is the same as that described in Fig. 2. (a) Nonreducing glucose residue bound to monomer C. (b) Fo − Fc electron density map (green), calculated by omitting the sugars (3.0σ) showing laminaritriose monomer C. (c) The reducing and central glucose residues visible in monomer B. (d) Fo − Fc electron density omit maps of langerin CRD bound to laminaritriose monomer B. Map contours at 3.0σ and 2.2σ are shown in blue and green, respectively.

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


Structural basis for langerin recognition of diverse pathogen and mammalian glycans through a single binding site.

Feinberg H, Taylor ME, Razi N, McBride R, Knirel YA, Graham SA, Drickamer K, Weis WI - J. Mol. Biol. (2010)

Structure of the CRD of langerin bound to laminaritriose. The color scheme is the same as that described in Fig. 2. (a) Nonreducing glucose residue bound to monomer C. (b) Fo − Fc electron density map (green), calculated by omitting the sugars (3.0σ) showing laminaritriose monomer C. (c) The reducing and central glucose residues visible in monomer B. (d) Fo − Fc electron density omit maps of langerin CRD bound to laminaritriose monomer B. Map contours at 3.0σ and 2.2σ are shown in blue and green, respectively.
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Related In: Results  -  Collection

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Show All Figures
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f0020: Structure of the CRD of langerin bound to laminaritriose. The color scheme is the same as that described in Fig. 2. (a) Nonreducing glucose residue bound to monomer C. (b) Fo − Fc electron density map (green), calculated by omitting the sugars (3.0σ) showing laminaritriose monomer C. (c) The reducing and central glucose residues visible in monomer B. (d) Fo − Fc electron density omit maps of langerin CRD bound to laminaritriose monomer B. Map contours at 3.0σ and 2.2σ are shown in blue and green, respectively.
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

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Structural Biology, Stanford University School of Medicine, Stanford, CA, USA.

Show MeSH
Related in: MedlinePlus