Plasmodium reichenowi EBA-140 merozoite ligand binds to glycophorin D on chimpanzee red blood cells, shedding new light on origins of Plasmodium falciparum

Zerka, Agata; Kaczmarek, Radosław; Czerwiński, Marcin; Jaśkiewicz, Ewa

doi:10.1186/s13071-017-2507-8

Cited by 6 publications

(4 citation statements)

References 50 publications

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“…The identity of the recognized sialoprotein also differs between P. reichenowi and P. falciparum. While Pf EBA-140 binds to glycophorin C as described above, the P. reichenowi homolog interacts with glycophorin D (Zerka et al, 2017). These observations favor a model in which humans and P. falciparum co-evolved and P. falciparum's ability to preferentially recognize Neu5Accontaining proteins led to its emergence as the most deadly human parasite (Martin et al, 2005;Proto et al, 2019).…”

Section: Sialic-acid-containing Glycansmentioning

confidence: 92%

Unveiling the Sugary Secrets of Plasmodium Parasites

2021

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Plasmodium parasites cause malaria disease, one of the leading global health burdens for humanity, infecting hundreds of millions of people each year. Different glycans on the parasite and the host cell surface play significant roles in both malaria pathogenesis and host defense mechanisms. So far, only small, truncated N- and O-glycans have been identified in Plasmodium species. In contrast, complex glycosylphosphatidylinositol (GPI) glycolipids are highly abundant on the parasite’s cell membrane and are essential for its survival. Moreover, the parasites express lectins that bind and exploit the host cell surface glycans for different aspects of the parasite life cycle, such as adherence, invasion, and evasion of the host immune system. In parallel, the host cell glycocalyx and lectin expression serve as the first line of defense against Plasmodium parasites and directly dictate susceptibility to Plasmodium infection. This review provides an overview of the glycobiology involved in Plasmodium-host interactions and its contribution to malaria pathogenesis. Recent findings are presented and evaluated in the context of potential therapeutic exploitation.

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Section: Sialic-acid-containing Glycansmentioning

confidence: 92%

Unveiling the Sugary Secrets of Plasmodium Parasites

2021

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“…The glycophorin D (a truncated form of GPC) was identified as receptor for P . reichenowi EBA-140 ligand [ 60 ] ( Figure 2 ).…”

Section: Sialic Acidsmentioning

confidence: 99%

“…The ape homologues of the EBA P. falciparum ligands, including chimpanzee P . reichenowi , have been identified [ 60 , 62 ]. It was shown that the receptors for P .…”

Section: Sialic Acidsmentioning

confidence: 99%

Red Blood Cells Oligosaccharides as Targets for Plasmodium Invasion

et al. 2022

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The key element in developing a successful malaria treatment is a good understanding of molecular mechanisms engaged in human host infection. It is assumed that oligosaccharides play a significant role in Plasmodium parasites binding to RBCs at different steps of host infection. The formation of a tight junction between EBL merozoite ligands and glycophorin receptors is the crucial interaction in ensuring merozoite entry into RBCs. It was proposed that sialic acid residues of O/N-linked glycans form clusters on a human glycophorins polypeptide chain, which facilitates the binding. Therefore, specific carbohydrate drugs have been suggested as possible malaria treatments. It was shown that the sugar moieties of N-acetylneuraminyl-N-acetate-lactosamine and 2,3-didehydro-2-deoxy-N-acetylneuraminic acid (DANA), which is its structural analog, can inhibit P. falciparum EBA-175-GPA interaction. Moreover, heparin-like molecules might be used as antimalarial drugs with some modifications to overcome their anticoagulant properties. Assuming that the principal interactions of Plasmodium merozoites and host cells are mediated by carbohydrates or glycan moieties, glycobiology-based approaches may lead to new malaria therapeutic targets.

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“…As discussed above, there is a general agreement that GPC but not GPD is P. falciparum EBA-140 receptor on human RBCs [79, 81–83, 97, 98]. However, evaluation of the binding of the homologous P. reichenowi EBA-140 ligand binding to chimpanzee RBCs [99] unexpectedly demonstrated that the chimpanzee homolog of human GPD is probably the receptor for that ligand [4, 100]. It may be hypothesized that GPD is an ancestral EBA-140 receptor in non-human primates, while GPC emerged as a new receptor for P. falciparum in humans.…”

Section: Introductionmentioning

confidence: 99%

Erythrocyte glycophorins as receptors for Plasmodium merozoites

et al. 2019

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Glycophorins are heavily glycosylated sialoglycoproteins of human and animal erythrocytes. In humans, there are four glycophorins: A, B, C and D. Glycophorins play an important role in the invasion of red blood cells (RBCs) by malaria parasites, which involves several ligands binding to RBC receptors. Four Plasmodium falciparum merozoite EBL ligands have been identified: erythrocyte-binding antigen-175 (EBA-175), erythrocyte-binding antigen-181 (EBA-181), erythrocyte-binding ligand-1 (EBL-1) and erythrocyte-binding antigen-140 (EBA-140). It is generally accepted that glycophorin A (GPA) is the receptor for P. falciparum EBA-175 ligand. It has been shown that α(2,3) sialic acid residues of GPA O-glycans form conformation-dependent clusters on GPA polypeptide chain which facilitate binding. P. falciparum can also invade erythrocytes using glycophorin B (GPB), which is structurally similar to GPA. It has been shown that P. falciparum EBL-1 ligand binds to GPB. Interestingly, a hybrid GPB-GPA molecule called Dantu is associated with a reduced risk of severe malaria and ameliorates malaria-related morbidity. Glycophorin C (GPC) is a receptor for P. falciparum EBA-140 ligand. Likewise, successful binding of EBA-140 depends on sialic acid residues of N- and O-linked oligosaccharides of GPC, which form a cluster or a conformational structure depending on the presence of peptide fragment encompassing amino acids (aa) 36–63. Evaluation of the homologous P. reichenowi EBA-140 unexpectedly revealed that the chimpanzee homolog of human glycophorin D (GPD) is probably the receptor for this ligand. In this review, we concentrate on the role of glycophorins as erythrocyte receptors for Plasmodium parasites. The presented data support the long-lasting idea of high evolutionary pressure exerted by Plasmodium on the human glycophorins, which emerge as important receptors for these parasites.

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Plasmodium reichenowi EBA-140 merozoite ligand binds to glycophorin D on chimpanzee red blood cells, shedding new light on origins of Plasmodium falciparum

Cited by 6 publications

References 50 publications

Unveiling the Sugary Secrets of Plasmodium Parasites

Unveiling the Sugary Secrets of Plasmodium Parasites

Red Blood Cells Oligosaccharides as Targets for Plasmodium Invasion

Erythrocyte glycophorins as receptors for Plasmodium merozoites

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