Probing the pH-dependency of DC-SIGN/R based multivalent lectin-glycan interactions using polyvalent glycan-gold nanoparticles

21 December 2023, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


The dendritic cell tetrameric lectin, DC-SIGN, and its closely related endothelial cell lectin, DC-SIGNR, (collectively as DC-SIGN/R) play a key role in the binding and transmission of deadly viruses, including Ebola, HIV, HCV, and SARS-CoV-2. Their virus binding/release processes involve a gradually acidifying environment following the natural intracellular trafficking pathways. Therefore, understanding their pH-dependent binding properties with glycan ligands is of great importance. We have recently developed densely glycosylated gold nanoparticles (glycan-GNPs) as a powerful new tool for probing DC-SIGN/R multivalent lectin-glycan interaction (MLGI) mechanisms. It not only can provide quantitative MLGI affinities but also important structural information, such as binding site orientation and binding modes. Herein, we further employ the glycan-GNP probes to investigate the pH dependency of DC-SIGN/R MLGI properties. We find that DC-SIGN/R MLGIs exhibit distinct pH dependence over the normal physiological (7.4) to lysosomal (∼4.6) pH range. DC-SIGN binds glycan-GNPs strongly and stably from pH 7.4-5.4, but the binding is weakened significantly as pH decreases to < 5.4. This is fully consistent with DC-SIGN’s role as an endocytic recycling receptor. In contrast, DC-SIGNR’s affinity with glycan-GNPs is enhanced with the decreasing pH from 7.4 to 5.4, peaking at pH 5.4, and then reduced as pH is further lowered. Moreover, both DC-SIGN/R binding with glycan-GNPs are found to be partially reversible in a pH-dependent manner.


pH dependence
multivalent lectin-glycan interaction
gold nanoparticle
fluorescence quenching

Supplementary materials

Supporting Information
Detailed experimental procedures and supporting figures


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