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EPCR

NOT Open Access | Decoding the Host-Parasite Protein Interactions Involved in Cerebral Malaria Through Glares of Molecular Dynamics Simulations

January 12, 2022 - 20:06 -- NOT Open Access
Author(s): 
Indari O, Sk MF, Jakhmola S, Jonniya NA, Jha HC, Kar P
Reference: 
J Phys Chem B. 2022 Jan 6

Malaria causes millions of deaths every year. The malaria parasite spends a substantial part of its life cycle inside human erythrocytes. Inside erythrocytes, it synthesizes and displays various proteins onto the erythrocyte surface, such as Plasmodium falciparum erythrocytic membrane protein-1 (PfEMP1). This protein contains cysteine-rich interdomain region (CIDR) domains which have many subtypes based on sequence diversity and can cross-talk with host molecules. The CIDRα1.4 subtype can attach host endothelial protein C receptor (EPCR).

Sickle-trait hemoglobin reduces adhesion to both CD36 and EPCR by Plasmodium falciparum-infected erythrocytes

June 16, 2021 - 14:58 -- Open Access
Author(s): 
Petersen JEV, Saelens JW, Freedman E, Turner L, Lavstsen T, Fairhurst RM, Diakité M, Taylor SM
Reference: 
PLoS Pathog. 2021 Jun 11;17(6):e1009659

Sickle-trait hemoglobin protects against severe Plasmodium falciparum malaria. Severe malaria is governed in part by the expression of the Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) that are encoded by var genes, specifically those variants that bind Endothelial Protein C Receptor (EPCR). In this study, we investigate the effect of sickle-trait on parasite var gene expression and function in vitro and in field-collected parasites.

Plasmodium falciparum erythrocyte membrane protein 1 variants induce cell swelling and disrupt the blood-brain barrier in cerebral malaria

March 2, 2021 - 15:15 -- Open Access
Author(s): 
Adams Y, Olsen RW, Jensen ATR, et al.
Reference: 
J Exp Med. 2021 Mar 1;218(3):e20201266

Cerebral malaria (CM) is caused by the binding of Plasmodium falciparum-infected erythrocytes (IEs) to the brain microvasculature, leading to inflammation, vessel occlusion, and cerebral swelling. We have previously linked dual intercellular adhesion molecule-1 (ICAM-1)- and endothelial protein C receptor (EPCR)-binding P. falciparum parasites to these symptoms, but the mechanism driving the pathogenesis has not been identified.

Structure-Guided Design of a Synthetic Mimic of an Endothelial Protein C Receptor-Binding PfEMP1 Protein

January 12, 2021 - 15:06 -- Open Access
Author(s): 
Barber NM, Lau CKY, Turner L, Watson G, Thrane S, Lusingu JPA, Lavstsen T, Higgins MK
Reference: 
mSphere. 2021 Jan 6;6(1):e01081-20

Structure-guided vaccine design provides a route to elicit a focused immune response against the most functionally important regions of a pathogen surface. This can be achieved by identifying epitopes for neutralizing antibodies through structural methods and recapitulating these epitopes by grafting their core structural features onto smaller scaffolds. In this study, we conducted a modified version of this protocol. We focused on the PfEMP1 protein family found on the surfaces of erythrocytes infected with Plasmodium falciparum A subset of PfEMP1 proteins bind to endothelial protein C receptor (EPCR), and their expression correlates with development of the symptoms of severe malaria.

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