%0 Journal Article
%9 ACL : Articles dans des revues avec comité de lecture répertoriées par l'AERES
%A Lennartz, F.
%A Adams, Y.
%A Bengtsson, A.
%A Olsen, R. W.
%A Turner, L.
%A Tuikue Ndam, Nicaise
%A Ecklu-Mensah, G.
%A Moussiliou, A.
%A Ofori, M. F.
%A Gamain, B.
%A Lusingu, J. P.
%A Petersen, J. E. V.
%A Wang, C. W.
%A Nunes-Silva, S.
%A Jespersen, J. S.
%A Lau, C. K. Y.
%A Theander, T. G.
%A Lavstsen, T.
%A Hviid, L.
%A Higgins, M. K.
%A Jensen, A. T. R.
%T Structure-guided identification of a family of dual receptor-binding PfEMP1 that is associated with cerebral malaria
%D 2017
%L fdi:010069279
%G ENG
%J Cell Host and Microbe
%@ 1931-3128
%M ISI:000396375600025
%N 3
%P 403-414
%R 10.1016/j.chom.2017.02.009
%U https://www.documentation.ird.fr/hor/fdi:010069279
%> https://www.documentation.ird.fr/intranet/publi/2017/03/010069279.pdf
%V 21
%W Horizon (IRD)
%X 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.
%$ 052 ; 050