ArticleThe Journal of biological chemistry2016
The Carbohydrate-linked Phosphorylcholine of the Parasitic Nematode Product ES-62 Modulates Complement Activation.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Bifunctional glycolipids targeting TLR4·MD-2 and short pentraxins.RSC chemical biology · 2026Article
- Glycan Complexity and Heterogeneity of Glycoproteins in Somatic Extracts and Secretome of the Infective Stage of the Helminth Fasciola hepatica.Molecular & cellular proteomics : MCP · 2023Article
- Defining the filarial N-glycoproteome by glycosite mapping in the human parasitic nematode Brugia malayi.Scientific reports · 2023Article
- C-reactive protein binds to short phosphoglycan repeats ofFrontiers in immunology · 2023Article
- Unraveling cross-reactivity of anti-glycan IgG responses in filarial nematode infections.Frontiers in immunology · 2023Article
- Functional Diversity of the Excretory/Secretory Proteins of Nematode Parasites.Acta parasitologica · 2022Review
- Mass Spectrometric and Glycan Microarray-Based Characterization of the Filarial Nematode Brugia malayi Glycome Reveals Anionic and Zwitterionic Glycan Antigens.Molecular & cellular proteomics : MCP · 2022Article
- Effect of New 2-Thioxoimidazolidin-4-one Compounds againstThe Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale · 2022Article
- Complement C4, Infections, and Autoimmune Diseases.Frontiers in immunology · 2021Review
- Zwitterionic Phosphodiester-Substituted Neoglycoconjugates as Ligands for Antibodies and Acute Phase Proteins.ACS chemical biology · 2020Article
- Site-specific glycoproteomic characterization of ES-62: The major secreted product of the parasitic worm Acanthocheilonema viteae.Glycobiology · 2019Article
- Highly modified and immunoactive N-glycans of the canine heartworm.Nature communications · 2019Article
- Article
- A Trypsin-Sensitive Proteoglycan from the Tapeworm Hymenolepis diminuta Inhibits Murine Neutrophil Chemotaxis in vitro by Suppressing p38 MAP Kinase Activation.Journal of innate immunity · 2019Article
- A comprehensive Caenorhabditis elegans N-glycan shotgun array.Glycobiology · 2018Article
- C-Reactive Protein as a Therapeutic Target in Age-Related Macular Degeneration.Frontiers in immunology · 2018Review
- Functional Transformation of C-reactive Protein by Hydrogen Peroxide.The Journal of biological chemistry · 2017Article
- Parasite-Derived Proteins for the Treatment of Allergies and Autoimmune Diseases.Frontiers in microbiology · 2017Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Parasitic nematodes manufacture various carbohydrate-linked phosphorylcholine (PCh)-containing molecules, including ES-62, a protein with an N-linked glycan terminally substituted with PCh. The PCh component is biologically important because it is required for immunomodulatory effects. We showed that most ES-62 was bound to a single protein, C-reactive protein (CRP), in normal human serum, displaying a calcium-dependent, high-avidity interaction and ability to form large complexes. Unexpectedly, CRP binding to ES-62 failed to efficiently activate complement as far as the C3 convertase stage in comparison with PCh-BSA and PCh-containing Streptococcus pneumoniae cell wall polysaccharide. C1q capture assays demonstrated an ES-62-CRP-C1q interaction in serum. The three ligands all activated C1 and generated C4b to similar extents. However, a C2a active site was not generated following ES-62 binding to CRP, demonstrating that C2 cleavage was far less efficient for ES-62-containing complexes. We proposed that failure of C2 cleavage was due to the flexible nature of carbohydrate-bound PCh and that reduced proximity of the C1 complex was the reason that C2 was poorly cleaved. This was confirmed using synthetic analogues that were similar to ES-62 only in respect of having a flexible PCh. Furthermore, ES-62 was shown to deplete early complement components, such as the rate-limiting C4, following CRP interaction and thereby inhibit classical pathway activation. Thus, flexible PCh-glycan represents a novel mechanism for subversion of complement activation. These data illustrate the importance of the rate-limiting C4/C2 stage of complement activation and reveal a new addition to the repertoire of ES-62 immunomodulatory mechanisms with possible therapeutic applications.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.