A Thioredoxin Homologous Protein of Plasmodium falciparum Participates in Erythrocyte Invasion.

Wei Wang,Ning Jiang,Mats Wahlgren,Kai Zhang,Dongchao Zhang,Dawei Wang,Qijun Chen,Peng Huang,Huijun Lu,John H Adams

doi:10.1128/iai.00289-18

Wei Wang, Ning Jiang + Show 8 more

Open Access

https://doi.org/10.1128/iai.00289-18

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Abstract

Invasion of erythrocytes by merozoites is required in the life cycle of malarial parasites. Proteins derived from the invasive merozoites are essential ligands for erythrocyte recognition and penetration. In this study, we report a novel protein that possesses a Trx domain-like structure of the thioredoxin family and is expressed on the surface of merozoites of the malaria parasite Plasmodium falciparum This protein, namely, PfTrx-mero protein, displayed a mutated sequence character at the Trx domain, but with a specific binding activity to human erythrocytes. Specific antibodies to the protein inhibited merozoite invasion into human erythrocytes. Immunization with a homologous protein of Plasmodium berghei strain ANKA also showed significant protection against lethal infection in mice. These results suggested that the novel PfTrx-like-mero protein expressed on the surface of merozoites is an important ligand participating in erythrocyte invasion and a potential vaccine candidate.

Highlights

Invasion of erythrocytes by merozoites is required in the life cycle of malarial parasites
Thioredoxins (Trx), which exist in most known organisms, are proteins that act as antioxidants by facilitating the reduction of other proteins by cysteine thiol-disulfide exchange
In a recent study [13], from the heparin-binding proteome we identified a novel Trx-like protein in P. falciparum, which shows a similarity in general sequence and characteristics to Trx proteins but lacks the “-CXXC-” motif, which is the core for antioxidation function (Fig. 1)

Summary

Introduction

Invasion of erythrocytes by merozoites is required in the life cycle of malarial parasites. We report a novel protein that possesses a Trx domain-like structure of the thioredoxin family and is expressed on the surface of merozoites of the malaria parasite Plasmodium falciparum This protein, namely, PfTrx-mero protein, displayed a mutated sequence character at the Trx domain, but with a specific binding activity to human erythrocytes. Immunization with a homologous protein of Plasmodium berghei strain ANKA showed significant protection against lethal infection in mice These results suggested that the novel PfTrx-like-mero protein expressed on the surface of merozoites is an important ligand participating in erythrocyte invasion and a potential vaccine candidate. A novel protein encoded by PF3D7_1104400 was found to possess a conserved sequence feature of the Trx family It was expressed mainly at the merozoite surface and participated in erythrocyte invasion by binding to heparin sulfate receptors on the erythrocytes. The data revealed a novel function of the Trx family proteins in the malaria parasite P. falciparum

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