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

• DOI: 10.1016/j.chom.2017.02.009
• Publication Date: 2017-03-08T18:15:23Z
• Authors: Frank Lennartz; Yvonne Adams; Anja Bengtsson; Rebecca W. Olsen; Louise Turner; Nicaise T. Ndam; Gertrude Ecklu-Me...; Azizath Moussiliou; Michael F. Ofori; Benoit Gamain; John P. Lusingu; Jens E.V. Petersen; Christian W. Wang; Sofia Nunes-Silva; Jakob S. Jespersen; Clinton K.Y. Lau; Thor G. Theander; Thomas Lavstsen; Lars Hviid; Matthew K. Higgins; Anja T.R. Jensen
• Keywords: Cerebral Malaria

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