Basaran, R., Ning, X., Budhadev, D. et al. (3 more authors) (2024) Probing the pH-dependency of DC-SIGN/R multivalent lectin-glycan interactions using polyvalent glycan-gold nanoparticles. Nanoscale Advances. ISSN 2516-0230
Abstract
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 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. 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 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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | This is an author produced version of an article accepted for publication in Nanoscale Advances, made available under the terms of the Creative Commons Attribution License (CC-BY), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | pH dependence, multivalent lectin-glycan interaction, glycoconjugate, gold nanoparticle, fluorescence quenching |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Chemistry (Leeds) > Inorganic Chemistry (Leeds) |
Funding Information: | Funder Grant number EPSRC (Engineering and Physical Sciences Research Council) EP/J501475/1 BBSRC (Biotechnology & Biological Sciences Research Council) BB/R007829/1 |
Depositing User: | Symplectic Publications |
Date Deposited: | 06 Mar 2024 14:38 |
Last Modified: | 14 Mar 2024 17:10 |
Status: | Published online |
Publisher: | The Royal Society of Chemistry |
Identification Number: | 10.1039/D3NA01013A |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:209924 |