Unique Binding Specificities of Proteins toward Isomeric Asparagine-Linked Glycans

Gao, Chao; Hanes, Melinda S.; Byrd-Leotis, Lauren; Wei, Mohui; Jia, Nan; Kardish, Robert; McKitrick, Tanya R.; Steinhauer, David A.; Cummings, Richard D.

doi:10.1016/j.chembiol.2019.01.002

Cited by 72 publications

(97 citation statements)

References 77 publications

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“…Microarray analyses on the complex N-glycan array were conducted as reported previously 47 . The microarray slides were probed with Fc-tagged DC-SIGN and L-SIGN at 10 μg/ml diluted in 1% BSA (TSM with 0.05% Tween) and binding was detected with Alexa Fluor 488 labelled goat anti-human IgG (H+L) (Invitrogen) at 5 μg/ml.…”

Section: Methodsmentioning

confidence: 99%

SARS-CoV-2 Spike Protein Interacts with Multiple Innate Immune Receptors

Gao

Zeng

Jia

et al. 2020

Preprint

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111

149

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The spike (S) glycoprotein in the envelope of SARS-CoV-2 is densely glycosylated but the functions of its glycosylation are unknown. Here we demonstrate that S is recognized in a glycan-dependent manner by multiple innate immune receptors including the mannose receptor MR/CD206, DC-SIGN/CD209, L-SIGN/CD209L, and MGL/CLEC10A/CD301. Single-cell RNA sequencing analyses indicate that such receptors are highly expressed in innate immune cells in tissues susceptible to SARS-CoV-2 infection. Binding of the above receptors to S is characterized by affinities in the picomolar range and consistent with S glycosylation analysis demonstrating a variety of N- and O-glycans as receptor ligands. These results indicate multiple routes for SARS-CoV-2 to interact with human cells and suggest alternative strategies for therapeutic intervention.

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Section: Methodsmentioning

confidence: 99%

SARS-CoV-2 Spike Protein Interacts with Multiple Innate Immune Receptors

Gao

Zeng

Jia

et al. 2020

Preprint

Self Cite

111

149

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“…However, information on the exact relationship between the lectins and N-glycan variants is limited due to a lack of a variety of these structures on arrays. Using the new 32 N-Glycan Array created by Gao et al (2019), each individual lectin was seen to have preferences for different N-glycan structures. Wheat germ agglutinin (WGA) and Lens culinaris agglutinin (LCA) bound the biantennary and 2,2,6-triantennary forms but not to the 2,2,4-counterparts or tetra-antennary N-glycans, which suggests that these lectins prefer branching; among the N-glycan backbone-binding lectins, only LCA, Pisum sativum agglutinin (PSA), and Concanavalin A (ConA) can accommodate both the α2,3-and α2,6-linked sialic acid.…”

Section: Plant Lectins and Antibodies As Essential Tools For Probing mentioning

confidence: 99%

Glycan Microarrays as Chemical Tools for Identifying Glycan Recognition by Immune Proteins

et al. 2019

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Glycans and glycan binding proteins (GBPs or lectins) are essential components in almost every aspect of immunology. Investigations of the interactions between glycans and GBPs have greatly advanced our understanding of the molecular basis of these fundamental immunological processes. In order to better study the glycan-GBP interactions, microscope glass slide-based glycan microarrays were conceived and proved to be an incredibly useful and successful tool. A variety of methods have been developed to better present the glycans so that they mimic natural presentations. Breakthroughs in chemical biology approaches have also made available glycans with sophisticated structures that were considered practically impossible just a few decade ago. Glycan microarrays provide a wealth of valuable information in immunological studies. They allow for discovery of detailed glycan binding preferences or novel binding epitopes of known endogenous immune receptors, which can potentially lead to the discovery of natural ligands that carry the glycans. Glycan microarrays also serve as a platform to discover new GBPs that are vital to the process of infection and invasion by microorganisms. This review summarizes the construction strategies and the immunological applications of glycan microarrays, particularly focused on those with the most comprehensive sets of glycan structures. We also review new methods and technologies that have evolved. We believe that glycan microarrays will continue to benefit the growing research community with various interests in the field of immunology.

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“…The binding of WGA was unaffected as it recognizes core GlcNAc residues independent of fucosylation. 17 Fucotrim I and P-Fuc2F showed a highly similar profile, not affecting the binding of L-Pha, PNA, and MAL-II. Only the binding of SNA increased using these inhibitors.…”

mentioning

confidence: 81%

“…These branches can be terminated with galactose, recognized by PNA, or α2,6-and α2,3-linked sialic acids recognized by SNA and MAL-II, respectively. 17,18 Binding of LCA and PSA was decreased for all fucosylation inhibitors as they are core fucose dependent. The binding of WGA was unaffected as it recognizes core GlcNAc residues independent of fucosylation.…”

mentioning

confidence: 99%

Fluorinated Mannosides Inhibit Cellular Fucosylation.

Pijnenborg¹,

Rossing²,

Noga³

et al. 2020

Preprint

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Fucose sugars are expressed on mammalian cell membranes as part of glycoconjugates and mediates essential physiological processes. The aberrant expression of fucosylated glycans has been linked to pathologies such as cancer, inflammation, infection, and genetic disorders. Tools to modulate fucose expression on living cells are needed to elucidate the biological role of fucose sugars and the development of potential therapeutics. Herein, we report a novel class of fucosylation inhibitors directly targeting de novo GDP-fucose biosynthesis. We demonstrate that cell permeable fluorinated mannoside 1-phosphate derivatives (Fucotrim I & II) are metabolic prodrugs that are metabolized to their respective GDP-mannose derivatives and efficiently inhibit cellular fucosylation.

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Unique Binding Specificities of Proteins toward Isomeric Asparagine-Linked Glycans

Cited by 72 publications

References 77 publications

SARS-CoV-2 Spike Protein Interacts with Multiple Innate Immune Receptors

SARS-CoV-2 Spike Protein Interacts with Multiple Innate Immune Receptors

Glycan Microarrays as Chemical Tools for Identifying Glycan Recognition by Immune Proteins

Fluorinated Mannosides Inhibit Cellular Fucosylation.

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