Plasmodium falciparum infected erythrocytes can bind to host receptors integrins ?V?3 and ?V?6 through DBL?1_D4 domain of PFL2665c PfEMP1 protein.

ABSTRACT: Major complications and mortality from Plasmodium falciparum malaria are associated with cytoadhesion of parasite-infected erythrocytes (IE). The main parasite ligands for cytoadhesion are members of the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family. Interactions of different host receptor-ligand pairs may lead to various pathological outcomes, like placental or cerebral malaria. It has been shown previously that IE can bind integrin ?V?3. Using bead-immobilized PfEMP1 constructs, we have identified that the PFL2665c DBL?1_D4 domain binds to ?V?3 and ?V?6. A parasite line expressing PFL2665c binds to surface-immobilized ?V?3 and ?V?6; both are RGD motif-binding integrins. Interactions can be inhibited by cyloRGDFV peptide, an antagonist of RGD-binding integrins. This is a first, to the best of our knowledge, implication of a specific PfEMP1 domain for binding to integrins. These host receptors have important physiological functions in endothelial and immune cells; therefore, these results will contribute to future studies and a better understanding, at the molecular level, of the physiological outcome of interactions between IE and integrin receptors on the surface of host cells.

SUBMITTER: Chesnokov O 

PROVIDER: S-EPMC6294747 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature