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Binding of Plasmodium falciparum merozoite surface proteins DBLMSP and DBLMSP2 to human immunoglobulin M is conserved amongst broadly diverged sequence variants.

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Crosnier, Cécile, Iqbal, Zamin, Knuepfer, Ellen, Maciuca, Sorina, Perrin, Abigail J, Kamuyu, Gathoni, Goulding, David, Bustamante, Leyla Y, Miles, Alistair, Moore, Shona C., Dougan, Gordon, Holder, Anthony A, Kwiatkowski, Dominic P, Rayner, Julian C, Pleass, Richard ORCID: https://orcid.org/0000-0001-7438-8296 and Wright, Gavin J (2016) 'Binding of Plasmodium falciparum merozoite surface proteins DBLMSP and DBLMSP2 to human immunoglobulin M is conserved amongst broadly diverged sequence variants.'. The Journal of Biological Chemistry, Vol 291, Issue 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 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. While 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
Subjects: QU Biochemistry > Genetics > QU 500 Genetic phenomena
QU Biochemistry > Proteins. Amino Acids. Peptides > QU 55 Proteins
QX Parasitology > Protozoa > QX 135 Plasmodia
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 765 Prevention and control
Faculty: Department: Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI): https://doi.org/10.1074/jbc.M116.722074
Depositing User: Jessica Jones
Date Deposited: 31 May 2016 10:52
Last Modified: 06 Feb 2018 13:12
URI: http://archive.lstmed.ac.uk/id/eprint/5905

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