The dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) is an innate immune C-type lectin receptor that recognizes carbohydrate-based pathogen associated with molecular patterns of various bacteria, fungi, viruses and protozoa. Although a range of highly mannosylated glycoproteins have been shown to induce signaling via DC-SIGN, precise structure of the recognized oligosaccharide epitope is still unclear. Using the array of oligosaccharides related to selected fragments of main fungal antigenic polysaccharides we revealed a highly specific pentamannoside ligand of DC-SIGN, consisting of α-(1→2)-linked mannose chains with one inner α-(1→3)-linked unit. This structural motif is present in Candida albicans cell wall mannan and corresponds to its antigenic factors 4 and 13b. This epitope is not ubiquitous in other yeast species and may account for the species-specific nature of fungal recognition via DC-SIGN. The discovered highly specific oligosaccharide ligands of DC-SIGN are tractable tools for interdisciplinary investigations of mechanisms of fungal innate immunity and anti-Candida defense. Ligand- and receptor-based NMR data demonstrated the pentasaccharide-to-DC-SIGN interaction in solution and enabled the deciphering of the interaction topology.

DC-SIGN, glycoarray, Candida albicans mannan, NMR binding and conformational studies, oligomannoside ligand

SMILES errors: -6)aDManp(1-6)[aDManp(1-2)]aDManp(1-6)[aDManp(1-2)aDManp(1-2)]aDManp(1-6)[/aDManp(1-2)/n=2/aDManp(1-2)]aDManp(1-6)[aDManp(1-3)/aDManp(1-2)/n=2/aDManp(1-2)]aDManp(1-6)[aDManp(1-2)aDManp(1-3)/aDManp(1-2)/n=2/aDManp(1-2)]aDManp(1-6)[aDManp(1-3)[aDManp(1-6)]aDManp(1-2)aDManp(1-2)aDManp(1-2)]aDManp(1-6)[aDManp(1-2)aDManp(1-3)[aDManp(1-6)]aDManp(1-2)aDManp(1-2)aDManp(1-2)]aDManp(1-6)[bDManp(1-2)/aDManp(1-2)/n=2/aDManp(1-2)]aDManp(1-6)[/bDManp(1-2)/n=2//aDManp(1-2)/n=2/aDManp(1-2)]aDManp(1-6)[/bDManp(1-2)/n=3//aDManp(1-2)/n=2/aDManp(1-2)]aDManp(1-6)[/bDManp(1-2)/n=4//aDManp(1-2)/n=2/aDManp(1-2)]aDManp(1-6)[aDManp(1-2)[bDManp(1-2)/bDManp(1-2)/n=0-2/aDManp(1-P-6)]aDManp(1-2)aDManp(1-2)]aDManp(1-:
SMILES error: number of atoms (~741) exceeds a structural formula limit (500)

The dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) is an innate immune C-type lectin receptor that recognizes carbohydrate-based pathogen associated with molecular patterns of various bacteria, fungi, viruses and protozoa. Although a range of highly mannosylated glycoproteins have been shown to induce signaling via DC-SIGN, precise structure of the recognized oligosaccharide epitope is still unclear. Using the array of oligosaccharides related to selected fragments of main fungal antigenic polysaccharides we revealed a highly specific pentamannoside ligand of DC-SIGN, consisting of α-(1→2)-linked mannose chains with one inner α-(1→3)-linked unit. This structural motif is present in Candida albicans cell wall mannan and corresponds to its antigenic factors 4 and 13b. This epitope is not ubiquitous in other yeast species and may account for the species-specific nature of fungal recognition via DC-SIGN. The discovered highly specific oligosaccharide ligands of DC-SIGN are tractable tools for interdisciplinary investigations of mechanisms of fungal innate immunity and anti-Candida defense. Ligand- and receptor-based NMR data demonstrated the pentasaccharide-to-DC-SIGN interaction in solution and enabled the deciphering of the interaction topology.

DC-SIGN, glycoarray, Candida albicans mannan, NMR binding and conformational studies, oligomannoside ligand

There is only one chemically distinct structure:

SVGMWSMILES3D molIonize

 

OC[C@H]1O[C@H](O)[C@@H](O[C@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]2O[C@H]2O[C@H](CO)[C@@H](O)[C@H](O[C@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]3O[C@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]3O)[C@@H]2O)[C@@H](O)[C@@H]1O

828.72 g/mol (C₃₀H₅₂O₂₆)