55 kDa Erythrocyte Membrane Protein

2020 ◽  
Author(s):  
Keyword(s):  
Membrane Protein ◽  
Erythrocyte Membrane ◽  
Erythrocyte Membrane Protein

Identifying targets of protective antibodies against severe malaria in Papua, Indonesia using locally expressed domains of Plasmodium falciparum Erythrocyte Membrane Protein 1.

2021 ◽  
Author(s):  
Janavi S Rambhatla ◽  
Gerry Q Tonkin-Hill ◽  
Eizo Takashima ◽  
Takafumi Tsuboi ◽  
Rintis Noviyanti ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Membrane Protein ◽  
Severe Malaria ◽  
Erythrocyte Membrane ◽  
Uncomplicated Malaria ◽  
Igg Antibodies ◽  
Erythrocyte Membrane Protein ◽  
African Children ◽  
Genes Encoding ◽  
Malaria Severity

Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), a diverse family of multi-domain proteins expressed on the surface of malaria-infected erythrocytes, is an important target of protective immunity against malaria. Our group recently studied transcription of the var genes encoding PfEMP1 in individuals from Papua, Indonesia with severe or uncomplicated malaria. We cloned and expressed domains from 32 PfEMP1s including 22 that were upregulated in severe malaria and 10 that were upregulated in uncomplicated malaria, using a wheat germ cell-free expression system. We used Luminex technology to measure IgG antibodies to these 32 domains and control proteins in 63 individuals (11 children). At presentation to hospital, levels of antibodies to PfEMP1 domains were either higher in uncomplicated malaria or were not significantly different between groups. Using principal components analysis, antibodies to three of 32 domains were highly discriminatory between groups. These included two domains upregulated in severe malaria, a DBLβ13 domain and a CIDRα1.6 domain (which has been previously implicated in severe malaria pathogenesis), and a DBLδ domain that was upregulated in uncomplicated malaria. Antibody to control non-PfEMP1 antigens did not differ with disease severity. Antibodies to PfEMP1 domains differ with malaria severity. Lack of antibodies to locally expressed PfEMP1 types, including both domains previously associated with severe malaria and newly identified targets, may in part explain malaria severity in Papuan adults. Importance Severe Plasmodium falciparum malaria kills many African children, and lack of antibody immunity predisposes to severe disease. A critical antibody target is the P. falciparum erythrocyte membrane 1 (PfEMP1) family of multidomain proteins, which are expressed on the infected erythrocyte surface and mediate parasite sequestration in deep organs. We previously identified var genes encoding PfEMP1 that were differentially expressed between severe and uncomplicated malaria in Papua, Indonesia. Here, we have expressed domains from 32 of these PfEMP1s and measured IgG antibody responses to them in Papuan adults and children. Using Principal Component Analysis, IgG antibodies to three domains distinguished between severe and uncomplicated malaria and were higher in uncomplicated malaria. Domains included CIDRα1.6, implicated in severe malaria; a DBLβ13 domain; and a DBLδ domain of unknown function. Immunity to locally relevant PfEMP1 domains may protect from severe malaria. Targets of immunity show important overlap between Asian adults and African children.

Carbamylation of normal and uremic erythrocyte membrane protein

1995 ◽  
Vol 28 (3) ◽  
pp. 332 ◽  
Author(s):  
Daniel J. Trepanier ◽  
Patrick S. Caines ◽  
Roger J. Thibert ◽  
Michael Goodwin ◽  
Thomas F. Draisey
Keyword(s):  
Membrane Protein ◽  
Erythrocyte Membrane ◽  
Erythrocyte Membrane Protein

scholarly journals DNA secondary structures are associated with recombination in major Plasmodium falciparum variable surface antigen gene families

2013 ◽  
Vol 42 (4) ◽  
pp. 2270-2281 ◽  
Author(s):  
Adam F. Sander ◽  
Thomas Lavstsen ◽  
Thomas S. Rask ◽  
Michael Lisby ◽  
Ali Salanti ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Membrane Protein ◽  
Erythrocyte Membrane ◽  
Gene Families ◽  
Secondary Structures ◽  
Erythrocyte Membrane Protein ◽  
Sexual Stages ◽  
Dna Secondary Structures ◽  
Parasitic Pathogens ◽  
Falciparum Erythrocyte Membrane Protein

Abstract Many bacterial, viral and parasitic pathogens undergo antigenic variation to counter host immune defense mechanisms. In Plasmodium falciparum, the most lethal of human malaria parasites, switching of var gene expression results in alternating expression of the adhesion proteins of the Plasmodium falciparum-erythrocyte membrane protein 1 class on the infected erythrocyte surface. Recombination clearly generates var diversity, but the nature and control of the genetic exchanges involved remain unclear. By experimental and bioinformatic identification of recombination events and genome-wide recombination hotspots in var genes, we show that during the parasite’s sexual stages, ectopic recombination between isogenous var paralogs occurs near low folding free energy DNA 50-mers and that these sequences are heavily concentrated at the boundaries of regions encoding individual Plasmodium falciparum-erythrocyte membrane protein 1 structural domains. The recombinogenic potential of these 50-mers is not parasite-specific because these sequences also induce recombination when transferred to the yeast Saccharomyces cerevisiae. Genetic cross data suggest that DNA secondary structures (DSS) act as inducers of recombination during DNA replication in P. falciparum sexual stages, and that these DSS-regulated genetic exchanges generate functional and diverse P. falciparum adhesion antigens. DSS-induced recombination may represent a common mechanism for optimizing the evolvability of virulence gene families in pathogens.

scholarly journals Identification of Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) as the Rosetting Ligand of the Malaria Parasite P. falciparum

1998 ◽  
Vol 187 (1) ◽  
pp. 15-23 ◽  
Author(s):  
Qijun Chen ◽  
Antonio Barragan ◽  
Victor Fernandez ◽  
Annika Sundström ◽  
Martha Schlichtherle ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Membrane Protein ◽  
Heparan Sulfate ◽  
Erythrocyte Membrane ◽  
Plasmodium Falciparum Malaria ◽  
Glutathione S Transferase ◽  
Binding Motifs ◽  
Erythrocyte Membrane Protein ◽  
Adhesive Interactions ◽  
Falciparum Erythrocyte Membrane Protein

Severe Plasmodium falciparum malaria is characterized by excessive sequestration of infected and uninfected erythrocytes in the microvasculature of the affected organ. Rosetting, the adhesion of P. falciparum–infected erythrocytes to uninfected erythrocytes is a virulent parasite phenotype associated with the occurrence of severe malaria. Here we report on the identification by single-cell reverse transcriptase PCR and cDNA cloning of the adhesive ligand P. falciparum erythrocyte membrane protein 1 (PfEMP1). Rosetting PfEMP1 contains clusters of glycosaminoglycan-binding motifs. A recombinant fusion protein (Duffy binding-like 1–glutathione S transferase; Duffy binding-like-1–GST) was found to adhere directly to normal erythrocytes, disrupt naturally formed rosettes, block rosette reformation, and bind to a heparin-Sepharose matrix. The adhesive interactions could be inhibited with heparan sulfate or enzymes that remove heparan sulfate from the cell surface whereas other enzymes or similar glycosaminoglycans of a like negative charge did not affect the binding. PfEMP1 is suggested to be the rosetting ligand and heparan sulfate, or a heparan sulfate–like molecule, the receptor both for PfEMP1 binding and naturally formed erythrocyte rosettes.

scholarly journals Immunization with Recombinant Plasmodium falciparum Erythrocyte Membrane Protein 1 CIDRα1 Domains Induces Domain Subtype Inhibitory Antibodies

2018 ◽  
Vol 86 (11) ◽  
Author(s):  
Louise Turner ◽  
Thor G. Theander ◽  
Thomas Lavstsen
Keyword(s):  
Plasmodium Falciparum ◽  
Membrane Protein ◽  
Erythrocyte Membrane ◽  
Sequence Similarity ◽  
Optimal Choice ◽  
Immune Recognition ◽  
Endothelial Protein C Receptor ◽  
Content Type ◽  
Erythrocyte Membrane Protein ◽  
Inhibitory Antibodies

ABSTRACT Plasmodium falciparum malaria pathogenesis is tied to the sequestration of parasites in the microvasculature. Parasite sequestration leading to severe malaria is mediated by P. falciparum erythrocyte membrane protein 1 (PfEMP1) binding to endothelial protein C receptor (EPCR) via its CIDRα1 domains. CIDRα1 domains are targets of naturally acquired immunity, and a vaccine eliciting antibodies inhibiting the EPCR binding of CIDRα1 could potentially prevent disease and death from malaria. CIDRα1 domains have diversified in sequence to escape immune recognition but preserved structure to maintain EPCR binding. The EPCR-binding CIDRα1 domains separate into six major sequence types predicted to form a conserved structure in which only the amino acids essential for EPCR binding are highly conserved. Here, we investigated whether antibodies elicited by vaccination with single or multiple recombinant CIDRα1 domains are able to bind and inhibit diverse CIDRα1 domains. We found that EPCR binding-inhibitory antibodies to CIDRα1 variants closely related to those used for vaccination are readily elicited, whereas antibodies binding distant CIDRα1 variants are sporadically generated and are rarely inhibitory. Despite this, sequence similarity correlated poorly with the ability of induced antibodies to inhibit across diverse variants, and no continuous sequence regions of importance for cross-inhibitory antibodies could be identified. This suggested that epitopes of cross-variant inhibitory antibodies were predominantly conformational. Vaccination with immunogens engineered to focus immune responses to specific epitopes or an optimal choice of multiple CIDRα1 variants may improve elicitation of broadly reactive and inhibitory antibody responses.

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