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

ABSTRACT: 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)? 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.

SUBMITTER: Cabrera A 

PROVIDER: S-EPMC6386811 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature