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Publication Abstract from PubMed

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.

Structure-Guided Identification of a Family of Dual Receptor-Binding PfEMP1 that Is Associated with Cerebral Malaria.,Lennartz F, Adams Y, Bengtsson A, Olsen RW, Turner L, Ndam NT, Ecklu-Mensah G, Moussiliou A, Ofori MF, Gamain B, Lusingu JP, Petersen JE, Wang CW, Nunes-Silva S, Jespersen JS, Lau CK, Theander TG, Lavstsen T, Hviid L, Higgins MK, Jensen AT Cell Host Microbe. 2017 Mar 8;21(3):403-414. doi: 10.1016/j.chom.2017.02.009. PMID:28279348^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.