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)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 language | English |
|---|---|
| Journal | The Journal of Infectious Diseases |
| Volume | 219 |
| Issue number | 6 |
| Pages (from-to) | 945-954 |
| Number of pages | 10 |
| ISSN | 0022-1899 |
| DOIs | |
| Publication status | Published - 23 Feb 2019 |
