{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Mukherjee R"],"funding":["Dutch Research Council (NWO)","Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Dutch Research Council)"],"pagination":["14745"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9737664"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["23(23)"],"pubmed_abstract":["Human milk oligosaccharides (HMOs) and their 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, (Le<sup>b</sup>) in a dose-dependent way. Interestingly, such inhibition by HMOS and 2'-FL was not detected for another C-type lectin, langerin, which is evolutionarily 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 Le<sup>b</sup>. Molecular dynamic (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. Le<sup>b</sup> has more flexible conformations and utilizes two binding modes, which operate one at a time via its two fucoses to bind to DC-SIGN. Our hypothesis is that 2'-FL may have a reduced entropic penalty due to its preorganized state, compared to Le<sup>b</sup>, and it has a lower binding enthalpy, suggesting a better binding to DC-SIGN. Thus, due to the better binding to DC-SIGN, 2'-FL may replace Le<sup>b</sup> from its binding pocket in DC-SIGN. The 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 the ligand-receptor interactions in possible immunomodulatory processes."],"journal":["International journal of molecular sciences"],"pubmed_title":["Human Milk Oligosaccharide 2'-Fucosyllactose Inhibits Ligand Binding to C-Type Lectin DC-SIGN but Not to Langerin."],"pmcid":["PMC9737664"],"funding_grant_id":["731.017.408"],"pubmed_authors":["van Bergenhenegouwen J","Somovilla VJ","Chiodo F","van Kooyk Y","Kraneveld AD","Bruijns S","Mukherjee R","Pieters RJ","Garssen J"],"additional_accession":[]},"is_claimable":false,"name":"Human Milk Oligosaccharide 2'-Fucosyllactose Inhibits Ligand Binding to C-Type Lectin DC-SIGN but Not to Langerin.","description":"Human milk oligosaccharides (HMOs) and their 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, (Le<sup>b</sup>) in a dose-dependent way. Interestingly, such inhibition by HMOS and 2'-FL was not detected for another C-type lectin, langerin, which is evolutionarily 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 Le<sup>b</sup>. Molecular dynamic (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. Le<sup>b</sup> has more flexible conformations and utilizes two binding modes, which operate one at a time via its two fucoses to bind to DC-SIGN. Our hypothesis is that 2'-FL may have a reduced entropic penalty due to its preorganized state, compared to Le<sup>b</sup>, and it has a lower binding enthalpy, suggesting a better binding to DC-SIGN. Thus, due to the better binding to DC-SIGN, 2'-FL may replace Le<sup>b</sup> from its binding pocket in DC-SIGN. The 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 the ligand-receptor interactions in possible immunomodulatory processes.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Nov","modification":"2026-04-08T11:33:33.146Z","creation":"2025-04-04T23:36:47.62Z"},"accession":"S-EPMC9737664","cross_references":{"pubmed":["36499067"],"doi":["10.3390/ijms232314745"]}}