Identification of a new DC-SIGN binding pentamannoside epitope within the complex structure of Candida albicans mannan

• Published in: Cell surface (Amsterdam) 2023-12, Vol.10, p.100109-100109, Article 100109
• Main Authors: Krylov, Vadim B., Gómez-Redondo, Marcos, Solovev, Arsenii S., Yashunsky, Dmitry V., Brown, Alistair J.P., Stappers, Mark H.T., Gow, Neil A.R., Ardá, Ana, Jiménez-Barbero, Jesús, Nifantiev, Nikolay E.
• Format: Article
• Language: English
• Subjects: Candida albicans mannan; DC-SIGN; Glycoarray; NMR binding and conformational studies; Oligomannoside ligand; Research Paper
• ISSN: 2468-2330; 2468-2330
• DOI: 10.1016/j.tcsw.2023.100109

[Display omitted] 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.