Issue 8, 2024

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

Abstract

The dendritic cell tetrameric lectin, DC-SIGN, and its closely related endothelial cell lectin, DC-SIGNR (collectively abbreviated 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 DC-SIGN/R's 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. They can provide not only 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 to ∼5.8, but the binding is weakened significantly as pH decreases to ≤5.4 and may be fully dissociated at pH 4.6. This behaviour 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. Interestingly, both DC-SIGN/R binding with glycan-GNPs are found to be partially reversible in a pH-dependent manner.

Graphical abstract: Probing the pH-dependency of DC-SIGN/R multivalent lectin–glycan interactions using polyvalent glycan-gold nanoparticles

Supplementary files

Article information

Article type
Paper
Submitted
18 11月 2023
Accepted
04 3月 2024
First published
11 3月 2024
This article is Open Access
Creative Commons BY license

Nanoscale Adv., 2024,6, 2198-2208

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

R. Basaran, X. Ning, D. Budhadev, N. Hondow, Y. Guo and D. Zhou, Nanoscale Adv., 2024, 6, 2198 DOI: 10.1039/D3NA01013A

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