Human Milk Oligosaccharide 2′-Fucosyllactose Inhibits Ligand Binding to C-Type Lectin DC-SIGN but Not to Langerin
| Autor: | Mukherjee, Reshmi, Somovilla, Victor J., Chiodo, Fabrizio, Bruijns, Sven, Pieters, Roland J., Garssen, Johan, van Kooyk, Yvette, Kraneveld, Aletta D., van Bergenhenegouwen, Jeroen, Afd Pharmacology, Afd Chemical Biology and Drug Discovery, Pharmacology, Chemical Biology and Drug Discovery |
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| Přispěvatelé: | Molecular cell biology and Immunology, AII - Cancer immunology, Afd Pharmacology, Afd Chemical Biology and Drug Discovery, Pharmacology, Chemical Biology and Drug Discovery |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Milk
Human Organic Chemistry Oligosaccharides Receptors Cell Surface General Medicine Ligands DC-SIGN Catalysis lewis B antigen Computer Science Applications Inorganic Chemistry langerin Humans 2′-FL Lectins C-Type human milk oligosaccharides Physical and Theoretical Chemistry Molecular Biology Spectroscopy Fucose |
| Zdroj: | International Journal of Molecular Sciences, 23(23):14745. Multidisciplinary Digital Publishing Institute (MDPI) Mukherjee, R, Somovilla, V J, Chiodo, F, Bruijns, S, Pieters, R J, Garssen, J, van Kooyk, Y, Kraneveld, A D & van Bergenhenegouwen, J 2022, ' Human Milk Oligosaccharide 2′-Fucosyllactose Inhibits Ligand Binding to C-Type Lectin DC-SIGN but Not to Langerin ', International Journal of Molecular Sciences, vol. 23, no. 23, 14745 . https://doi.org/10.3390/ijms232314745 International Journal of Molecular Sciences, 23(23). MDPI AG International Journal of Molecular Sciences; Volume 23; Issue 23; Pages: 14745 |
| ISSN: | 1661-6596 |
| DOI: | 10.3390/ijms232314745 |
| Popis: | Human milk oligosaccharides (HMOs) and its most abundant component, 2’-Fucosyllactose (2’-FL), are known to be immunomodulatory. Previously, it was shown that HMOs and 2’-FL bind to the C-type lectin receptor DC-SIGN. Here we show, using a ligand-receptor competition assay, that a whole mixture of HMOs from pooled human milk (HMOS) and 2’-FL inhibit the binding of the carbohydrate-binding receptor DC-SIGN to its prototypical ligands, fucose and the oligosaccharide Lewis-B, (Leb) in a dose-dependent way. Interestingly, such inhibition by HMOS and 2’-FL was not detected for another C-type lectin, Langerin, evolutionary similar to DC-SIGN. The cell-ligand competition assay using DC-SIGN expressing cells confirmed that 2’-FL inhibits the binding of DC-SIGN to Leb. Molecular dynamics (MD) simulations show that 2’-FL exists in a preorganized bioactive conformation before binding to DC-SIGN and this conformation is retained after binding to DC-SIGN. Leb has more flexible conformations and utilizes two binding modes, which operate one at a time via its two fucoses to bind to DC-SIGN. 2’-FL may have a reduced entropic penalty due to its preorganized state compared to Leb, and it has lower binding enthalpy, suggesting better binding to DC-SIGN. Thus, due to the better binding to DC-SIGN, 2’-FL may replace Leb from its binding pocket in DC-SIGN. MD simulations also showed that 2’-FL does not bind to Langerin. Our studies confirm 2’-FL as a specific ligand for DC-SIGN and suggest that 2’-FL can replace other DC-SIGN ligands from its binding pocket during ligand-receptor interactions in possible immunomodulatory processes. |
| Databáze: | OpenAIRE |
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