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Published on: March 10, 2021
HpBoRB, a helminth-derived CCP domain protein which binds RELMβ.
Vivien Shek1, Abhishek Jamwal2, Danielle J Smyth1
1Division of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dundee, the United Kingdom of Great Britain and Northern Ireland.
The intestinal nematode Heligmosomoides polygyrus bakeri (Hpb) secretes proteins that interact with host immunity. A newly identified Hpb protein, HpBoRB, binds to the anti-helminth protein resistin-like molecule beta (RELMβ), potentially evading host defenses.
Area of Science:
- Parasitology
- Immunology
- Molecular Biology
Background:
- Helminth infections establish by releasing immunomodulatory proteins to evade host immunity.
- The intestinal nematode Heligmosomoides polygyrus bakeri (Hpb) secretes numerous immunomodulatory proteins, many containing Complement Control Protein (CCP) domains.
Purpose of the Study:
- To identify novel Hpb-secreted proteins with immunomodulatory functions.
- To investigate potential interactions between Hpb proteins and host immune molecules.
Main Methods:
- Genome-wide identification of CCP domain-containing proteins in Hpb.
- Screening of cloned Hpb proteins for interactions with host immune proteins using Avidity-based Extracellular Interaction Screening (AVEXIS).
- Validation of interactions using ELISA, competition assays, size exclusion chromatography, and surface plasmon resonance.
Main Results:
- Confirmed known interactions between Hpb proteins (HpBARI, TGM1) and their targets (ST2, TGFBR2).
- Discovered a novel interaction between a 2 CCP domain Hpb protein, named HpBoRB, and mouse resistin-like molecule beta (RELMβ).
- HpBoRB exhibits specific, heat-labile binding to RELMβ with subnanomolar affinity.
Conclusions:
- Hpb secretes a diverse repertoire of CCP domain proteins, including novel interactors with host immune molecules.
- The newly identified HpBoRB protein may interfere with the anti-helminth function of RELMβ, contributing to parasite persistence.
- This study expands the understanding of host-parasite interactions mediated by secreted Hpb proteins.
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