Colomb, Florent, Jamwal, Abhishek, Ogunkanbi, Adefunke et al. (6 more authors) (2024) Heparan sulphate binding controls in vivo half-life of the HpARI protein family. eLife. RP9900. ISSN 2050-084X
Abstract
The parasitic nematode Heligmosomoides polygyrus bakeri secretes the HpARI family, which bind to IL-33, either suppressing (HpARI1 and HpARI2) or enhancing (HpARI3) responses to the cytokine. We previously showed that HpARI2 also bound to DNA via its first complement control protein (CCP1) domain. Here, we find that HpARI1 can also bind DNA, while HpARI3 cannot. Through the production of HpARI2/HpARI3 CCP1 domain-swapped chimeras, DNA-binding ability can be transferred, and correlates with in vivo half-life of administered proteins. We found that HpARI1 and HpARI2 (but not HpARI3) also binds to the extracellular matrix component heparan sulphate (HS), and structural modelling showed a basic charged patch in the CCP1 domain of HpARI1 and HpARI2 (but not HpARI3) which could facilitate these interactions. Finally, a mutant of HpARI2 was produced which lacked DNA and HS binding, and was also shown to have a short half-life in vivo. Therefore, we propose that during infection the suppressive HpARI1 and HpARI2 proteins have long-lasting effects at the site of deposition due to DNA and/or extracellular matrix interactions, while HpARI3 has a shorter half-life due to a lack of these interactions.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | Publisher Copyright: © 2024, Colomb et al. |
Keywords: | Heligmosoides polygyrus bakeri,heparan sulphate,IL-33,immunology,infectious disease,inflammation,microbiology,mouse |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Arts and Humanities (York) > Language and Linguistic Science (York) The University of York > Faculty of Sciences (York) > Centre for Immunology and Infection (CII) (York) The University of York > Faculty of Sciences (York) > Biology (York) |
Depositing User: | Pure (York) |
Date Deposited: | 05 Mar 2025 08:40 |
Last Modified: | 05 Mar 2025 08:40 |
Published Version: | https://doi.org/10.7554/eLife.99000 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.7554/eLife.99000 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:224056 |
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Filename: elife-99000-v1.pdf
Description: Heparan sulphate binding controls in vivo half-life of the HpARI protein family
Licence: CC-BY 2.5