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Plasmodium falciparum-CD36 Structure-Function Relationships Defined by Ortholog Scanning Mutagenesis

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DOI

  1. Meta-analysis of Plasmodium falciparum var Signatures Contributing to Severe Malaria in African Children and Indian Adults

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Cerebral malaria is associated with differential cytoadherence to brain endothelial cells

    Research output: Contribution to journalJournal articleResearchpeer-review

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BACKGROUND: The interaction of Plasmodium falciparum-infected erythrocytes (IEs) with the host receptor CD36 is among the most studied host-parasite interfaces. CD36 is a scavenger receptor that binds numerous ligands including the cysteine-rich interdomain region (CIDR)α domains of the erythrocyte membrane protein 1 family (PfEMP1) expressed on the surface of IEs. CD36 is conserved across species, but orthologs display differential binding of IEs.

METHODS: In this study, we exploited these differences, combined with the recent crystal structure and 3-dimensional modeling of CD36, to investigate malaria-CD36 structure-function relationships and further define IE-CD36 binding interactions.

RESULTS: We show that a charged surface in the membrane-distal region of CD36 is necessary for IE binding. Moreover, IE interaction with this binding surface is influenced by additional CD36 domains, both proximal to and at a distance from this site.

CONCLUSIONS: Our data indicate that subtle sequence and spatial differences in these domains modify receptor conformation and regulate the ability of CD36 to selectively interact with its diverse ligands.

Original languageEnglish
JournalThe Journal of infectious diseases
Volume219
Issue number6
Pages (from-to)945-954
Number of pages10
ISSN0022-1899
DOIs
Publication statusPublished - 23 Feb 2019

    Research areas

  • Animals, Antigens, Protozoan/metabolism, Binding Sites, CD36 Antigens/chemistry, CHO Cells, COS Cells, Chlorocebus aethiops, Cricetulus, Erythrocytes/parasitology, Host-Parasite Interactions/genetics, Humans, Malaria, Falciparum/immunology, Mutagenesis, Plasmodium falciparum/immunology, Structure-Activity Relationship

ID: 59239321