Binding of <i>Plasmodium falciparum</i> Merozoite Surface Proteins DBLMSP and DBLMSP2 to Human Immunoglobulin M Is Conserved among Broadly Diverged Sequence Variants



Crosnier, Cecile, Iqbal, Zamin, Knuepfer, Ellen, Maciuca, Sorina, Perrin, Abigail J, Kamuyu, Gathoni, Goulding, David, Bustamante, Leyla Y, Miles, Alistair, Moore, Shona C ORCID: 0000-0001-8610-2806
et al (show 6 more authors) (2016) Binding of <i>Plasmodium falciparum</i> Merozoite Surface Proteins DBLMSP and DBLMSP2 to Human Immunoglobulin M Is Conserved among Broadly Diverged Sequence Variants. JOURNAL OF BIOLOGICAL CHEMISTRY, 291 (27). pp. 14285-14299.

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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.

Item Type: Article
Uncontrolled Keywords: genetic polymorphism, host-pathogen interaction, parasite, plasmodium, protein-protein interaction, immunoglobulin M (IgM), merozoite
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User: Symplectic Admin
Date Deposited: 14 May 2021 15:31
Last Modified: 12 Oct 2023 12:02
DOI: 10.1074/jbc.M116.722074
Open Access URL: https://www.jbc.org/article/S0021-9258(20)36771-5/...
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3122732