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Structure-Guided Identification of a Family of Dual Receptor-Binding PfEMP1 that Is Associated with Cerebral Malaria.

Lennartz, F., Adams, Y., Bengtsson, A., Olsen, R. W., Turner, L., Ndam, N. T., Ecklu-Mensah, G., Moussiliou, A., Ofori, M. F., Gamain, B., Lusingu, J. P., Petersen, J. E. V., Wang, C. W., Nunes-Silva, S., Jespersen, J. S., Lau, C. K. Y., Theander, T. G., Lavstsen, T., Hviid, L., Higgins, M. K. and Jensen, A. T. R. (2017) Structure-Guided Identification of a Family of Dual Receptor-Binding PfEMP1 that Is Associated with Cerebral Malaria. Cell host & microbe, 21 (3). pp. 403-414. ISSN 1934-6069

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Abstract

Cerebral malaria is a deadly outcome of infection by Plasmodium falciparum, occurring when parasite-infected erythrocytes accumulate in the brain. These erythrocytes display parasite proteins of the PfEMP1 family that bind various endothelial receptors. Despite the importance of cerebral malaria, a binding phenotype linked to its symptoms has not been identified. Here, we used structural biology to determine how a group of PfEMP1 proteins interacts with intercellular adhesion molecule 1 (ICAM-1), allowing us to predict binders from a specific sequence motif alone. Analysis of multiple Plasmodium falciparum genomes showed that ICAM-1-binding PfEMP1s also interact with endothelial protein C receptor (EPCR), allowing infected erythrocytes to synergistically bind both receptors. Expression of these PfEMP1s, predicted to bind both ICAM-1 and EPCR, is associated with increased risk of developing cerebral malaria. This study therefore reveals an important PfEMP1-binding phenotype that could be targeted as part of a strategy to prevent cerebral malaria.

Item Type: Article
Keywords: EPCR, ICAM-1, PfEMP1, Plasmodium falciparum, Cerebral malaria
Subjects: Malaria > Surveillance, monitoring, evaluation
Malaria > Diagnosis & treatment
Divisions: National Institute for Medical Research
Depositing User: Mr Joseph Madata
Date Deposited: 10 Apr 2017 11:35
Last Modified: 10 Apr 2017 11:35
URI: http://ihi.eprints.org/id/eprint/4095

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