10779/crick.12657086.v1
Cécile Crosnier
Cécile
Crosnier
Zamin Iqbal
Zamin
Iqbal
Ellen Knuepfer
Ellen
Knuepfer
Sorina Maciuca
Sorina
Maciuca
Abigail J Perrin
Abigail J
Perrin
Gathoni Kamuyu
Gathoni
Kamuyu
David Goulding
David
Goulding
Leyla Y Bustamante
Leyla Y
Bustamante
Alistair Miles
Alistair
Miles
Shona C Moore
Shona C
Moore
Gordon Dougan
Gordon
Dougan
Anthony A Holder
Anthony A
Holder
Dominic P Kwiatkowski
Dominic P
Kwiatkowski
Julian C Rayner
Julian C
Rayner
Richard J Pleass
Richard J
Pleass
Gavin J Wright
Gavin J
Wright
Binding of Plasmodium falciparum merozoite surface proteins DBLMSP and DBLMSP2 to human immunoglobulin M is conserved amongst broadly diverged sequence variants
The Francis Crick Institute
2020
genetic polymorphism
host-pathogen interaction
immunoglobulin M (IgM)
merozoite
parasite
plasmodium
protein-protein interaction
Animals
Antigens, Protozoan
Humans
Immunoglobulin M
Plasmodium falciparum
Protein Binding
Protozoan Proteins
Holder FC001097
06 Biological Sciences
11 Medical and Health Sciences
03 Chemical Sciences
Biochemistry & Molecular Biology
2020-07-17 16:27:41
Journal contribution
https://crick.figshare.com/articles/journal_contribution/Binding_of_Plasmodium_falciparum_merozoite_surface_proteins_DBLMSP_and_DBLMSP2_to_human_immunoglobulin_M_is_conserved_amongst_broadly_diverged_sequence_variants/12657086
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.