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

Autor:	Lennartz F; Department of Biochemistry, University of Oxford, South Parks Road, OX1 3QU Oxford, UK., Adams Y; Centre for Medical Parasitology, Department of Immunology and Microbiology (ISIM), Faculty of Health and Medical Sciences, University of Copenhagen, 1165 Copenhagen, Denmark; Department of Infectious Diseases, Copenhagen University Hospital (Rigshospitalet), 2100 Copenhagen, Denmark., Bengtsson A; Centre for Medical Parasitology, Department of Immunology and Microbiology (ISIM), Faculty of Health and Medical Sciences, University of Copenhagen, 1165 Copenhagen, Denmark; Department of Infectious Diseases, Copenhagen University Hospital (Rigshospitalet), 2100 Copenhagen, Denmark., Olsen RW; Centre for Medical Parasitology, Department of Immunology and Microbiology (ISIM), Faculty of Health and Medical Sciences, University of Copenhagen, 1165 Copenhagen, Denmark; Department of Infectious Diseases, Copenhagen University Hospital (Rigshospitalet), 2100 Copenhagen, Denmark., Turner L; Centre for Medical Parasitology, Department of Immunology and Microbiology (ISIM), Faculty of Health and Medical Sciences, University of Copenhagen, 1165 Copenhagen, Denmark; Department of Infectious Diseases, Copenhagen University Hospital (Rigshospitalet), 2100 Copenhagen, Denmark., Ndam NT; Faculté de Pharmacie, Institut de Recherche pour le Développement (IRD), COMUE Sorbonne Paris Cité, 75013 Paris, France; Faculté des Sciences de la Santé (FSS), Université d'Aboméy Calavi, 01 BP 526 Cotonou, Benin., Ecklu-Mensah G; Centre for Medical Parasitology, Department of Immunology and Microbiology (ISIM), Faculty of Health and Medical Sciences, University of Copenhagen, 1165 Copenhagen, Denmark; Department of Infectious Diseases, Copenhagen University Hospital (Rigshospitalet), 2100 Copenhagen, Denmark; Department of Immunology, Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana., Moussiliou A; Faculté des Sciences de la Santé (FSS), Université d'Aboméy Calavi, 01 BP 526 Cotonou, Benin., Ofori MF; Department of Immunology, Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana., Gamain B; UMR_S1134, Université Sorbonne Paris Cité, Université Paris Diderot, Inserm, INTS, Unité Biologie Intégrée du Globule Rouge, Laboratoire d'Excellence GR-Ex, 75013 Paris, France., Lusingu JP; National Institute for Medical Research, Tanga Centre, 11101 Dar es Salaam, Tanzania., Petersen JE; Centre for Medical Parasitology, Department of Immunology and Microbiology (ISIM), Faculty of Health and Medical Sciences, University of Copenhagen, 1165 Copenhagen, Denmark; Department of Infectious Diseases, Copenhagen University Hospital (Rigshospitalet), 2100 Copenhagen, Denmark., Wang CW; Centre for Medical Parasitology, Department of Immunology and Microbiology (ISIM), Faculty of Health and Medical Sciences, University of Copenhagen, 1165 Copenhagen, Denmark; Department of Infectious Diseases, Copenhagen University Hospital (Rigshospitalet), 2100 Copenhagen, Denmark., Nunes-Silva S; UMR_S1134, Université Sorbonne Paris Cité, Université Paris Diderot, Inserm, INTS, Unité Biologie Intégrée du Globule Rouge, Laboratoire d'Excellence GR-Ex, 75013 Paris, France., Jespersen JS; Centre for Medical Parasitology, Department of Immunology and Microbiology (ISIM), Faculty of Health and Medical Sciences, University of Copenhagen, 1165 Copenhagen, Denmark; Department of Infectious Diseases, Copenhagen University Hospital (Rigshospitalet), 2100 Copenhagen, Denmark., Lau CK; Department of Biochemistry, University of Oxford, South Parks Road, OX1 3QU Oxford, UK., Theander TG; Centre for Medical Parasitology, Department of Immunology and Microbiology (ISIM), Faculty of Health and Medical Sciences, University of Copenhagen, 1165 Copenhagen, Denmark; Department of Infectious Diseases, Copenhagen University Hospital (Rigshospitalet), 2100 Copenhagen, Denmark., Lavstsen T; Centre for Medical Parasitology, Department of Immunology and Microbiology (ISIM), Faculty of Health and Medical Sciences, University of Copenhagen, 1165 Copenhagen, Denmark; Department of Infectious Diseases, Copenhagen University Hospital (Rigshospitalet), 2100 Copenhagen, Denmark., Hviid L; Centre for Medical Parasitology, Department of Immunology and Microbiology (ISIM), Faculty of Health and Medical Sciences, University of Copenhagen, 1165 Copenhagen, Denmark; Department of Infectious Diseases, Copenhagen University Hospital (Rigshospitalet), 2100 Copenhagen, Denmark., Higgins MK; Department of Biochemistry, University of Oxford, South Parks Road, OX1 3QU Oxford, UK. Electronic address: matthew.higgins@bioch.ox.ac.uk., Jensen AT; Centre for Medical Parasitology, Department of Immunology and Microbiology (ISIM), Faculty of Health and Medical Sciences, University of Copenhagen, 1165 Copenhagen, Denmark; Department of Infectious Diseases, Copenhagen University Hospital (Rigshospitalet), 2100 Copenhagen, Denmark. Electronic address: atrj@sund.ku.dk.
Jazyk:	angličtina
Zdroj:	Cell host & microbe [Cell Host Microbe] 2017 Mar 08; Vol. 21 (3), pp. 403-414.
DOI:	10.1016/j.chom.2017.02.009
Abstrakt:	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. (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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