Scarff, CA orcid.org/0000-0001-6168-0060, Thompson, RF, Newlands, GFJ et al. (8 more authors) (2020) Structure of the protective nematode protease complex H-gal-GP and its conservation across roundworm parasites. PLoS Pathogens, 16 (4). e1008465. ISSN 1553-7366
Abstract
Roundworm parasite infections are a major cause of human and livestock disease worldwide and a threat to global food security. Disease control currently relies on anthelmintic drugs to which roundworms are becoming increasingly resistant. An alternative approach is control by vaccination and ‘hidden antigens’, components of the worm gut not encountered by the infected host, have been exploited to produce Barbervax, the first commercial vaccine for a gut dwelling nematode of any host. Here we present the structure of H-gal-GP, a hidden antigen from Haemonchus contortus, the Barber’s Pole worm, and a major component of Barbervax. We demonstrate its novel architecture, subunit composition and topology, flexibility and heterogeneity using cryo-electron microscopy, mass spectrometry, and modelling. Importantly, we demonstrate that complexes with the same architecture are present in other Strongylid roundworm parasites including human hookworm. This suggests a common ancestry and the potential for development of a unified hidden antigen vaccine.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 Scarff et al. This is an open access article under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) (https://creativecommons.org/licenses/by/4.0/) |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) > Cryo EM, Image Processing (Leeds) |
Funding Information: | Funder Grant number Wellcome Trust 204825/Z/16/Z |
Depositing User: | Symplectic Publications |
Date Deposited: | 10 Mar 2020 14:29 |
Last Modified: | 25 Jun 2023 22:11 |
Status: | Published |
Publisher: | Public Library of Science (PLoS) |
Identification Number: | 10.1371/journal.ppat.1008465 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:158245 |