Crosnier, Cécile orcid.org/0000-0003-0619-9797, Iqbal, Zamin, Knuepfer, Ellen et al. (13 more authors) (2016) Binding of Plasmodium falciparum Merozoite Surface Proteins DBLMSP and DBLMSP2 to Human Immunoglobulin M Is Conserved among Broadly Diverged Sequence Variants. The Journal of biological chemistry. pp. 14285-14299. ISSN 1083-351X
Abstract
Diversity at pathogen genetic loci can be driven by host adaptive immune selection pressure and may reveal proteins important for parasite biology. Population-based genome sequencing of Plasmodium falciparum, the parasite responsible for the most severe form of malaria, has highlighted two related polymorphic genes called dblmsp and dblmsp2, which encode Duffy binding-like (DBL) domain-containing proteins located on the merozoite surface but whose function remains unknown. Using recombinant proteins and transgenic parasites, we show that DBLMSP and DBLMSP2 directly and avidly bind human IgM via their DBL domains. We used whole genome sequence data from over 400 African and Asian P. falciparum isolates to show that dblmsp and dblmsp2 exhibit extreme protein polymorphism in their DBL domain, with multiple variants of two major allelic classes present in every population tested. Despite this variability, the IgM binding function was retained across diverse sequence representatives. Although this interaction did not seem to have an effect on the ability of the parasite to invade red blood cells, binding of DBLMSP and DBLMSP2 to IgM inhibited the overall immunoreactivity of these proteins to IgG from patients who had been exposed to the parasite. This suggests that IgM binding might mask these proteins from the host humoral immune system. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Keywords: | first & last 3 (QQ only),first & last (all papers) |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Biology (York) The University of York > Faculty of Sciences (York) > Hull York Medical School (York) |
Depositing User: | Pure (York) |
Date Deposited: | 19 Oct 2020 15:40 |
Last Modified: | 21 Jan 2025 17:50 |
Published Version: | https://doi.org/10.1074/jbc.M116.722074 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1074/jbc.M116.722074 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:166880 |
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