HpBoRB, a helminth-derived CCP domain protein which binds RELMβ
bioRxiv (Cold Spring Harbor Laboratory)
Abstract
Abstract Helminth infections persist by influencing host immunity through the release of immunomodulatory proteins which prevent immune ejection. The intestinal nematode Heligmosomoides polygyrus bakeri (Hpb) secretes multiple families of immunomodulatory proteins, many of which are composed of consecutive Complement Control Protein (CCP) domains. We hypothesized that further CCP domain proteins are secreted by the parasite to interact with the host. We identified an unusually large number of CCP domain-containing proteins in the genome of Hpb, and cloned a range of these for screening in an Avidity-based Extracellular Interaction Screening (AVEXIS) assay, focussing on interactions with host immune proteins. This screen confirmed the binding of known immunomodulators (HpBARI, TGM1) for their targets (ST2, TGFBR2) and identified a new interaction between a 2 CCP domain Hpb protein and mouse resistin-like molecule beta (RELMβ), a host protein demonstrated to have anti-helminth properties. This protein was named Binder of RELMβ (HpBoRB). This interaction was confirmed in ELISA, competition assays, size exclusion chromatography and surface plasmon resonance experiments, identifying a subnanomolar affinity interaction between HpBoRB and RELMβ. These data may indicate that Hpb interferes with the potent anti-helminth host protein RELMβ and adds to our knowledge of the host-parasite interactions mediated by Hpb secreted proteins.
Authors 12
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Affiliation as printed
University of Dundee;
Division of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dundee, United Kingdom
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Affiliation as printed
University of Oxford;
Department of Biochemistry, University of Oxford, Oxford, United Kingdom
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Affiliation as printed
University of Dundee;
Division of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dundee, United Kingdom
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Affiliation as printed
University of Dundee;
Division of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dundee, United Kingdom
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Affiliation as printed
University of Dundee;
Division of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dundee, United Kingdom
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University of York · Hull York Medical School
Affiliation as printed
University of York;
Department of Biology, Hull York Medical School, York Biomedical Research Institute, University of York, York, United Kingdom
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University of Dundee · MRC Protein Phosphorylation and Ubiquitylation Unit
Affiliation as printed
MRC Protein Phosphorylation Unit;
MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK
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Affiliation as printed
University of Glasgow;
Centre for Parasitology, School of Infection and Immunity, University of Glasgow, University, Glasgow, G12 8TA, UK
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Affiliation as printed
University of Oxford;
Department of Biochemistry, University of Oxford, Oxford, United Kingdom
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Affiliation as printed
University of Edinburgh;
Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom
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Leiden University Medical Center
Affiliation as printed
Leiden University Medical Center
Department of Immunology, Leiden University Medical Center, Leiden, Netherlands
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Henry J. McSorley corresponding
Affiliation as printed
University of Dundee;
Division of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dundee, United Kingdom
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