Structure of a Plasmodium falciparum PfEMP1 rosetting domain reveals a role for the N-terminal segment in heparin-mediated rosette inhibition.

ABSTRACT: The human malaria parasite Plasmodium falciparum can cause infected red blood cells (iRBC) to form rosettes with uninfected RBC, a phenotype associated with severe malaria. Rosetting is mediated by a subset of the Plasmodium falciparum membrane protein 1 (PfEMP1) variant adhesins expressed on the infected host-cell surface. Heparin and other sulfated oligosaccharides, however, can disrupt rosettes, suggesting that therapeutic approaches to this form of severe malaria are feasible. We present a structural and functional study of the N-terminal domain of PfEMP1 from the VarO variant comprising the N-terminal segment (NTS) and the first DBL domain (DBL1α(1)), which is directly implicated in rosetting. We demonstrate that NTS-DBL1α(1)-VarO binds to RBC and that heparin inhibits this interactio

SUBMITTER: Juillerat A 

PROVIDER: S-EPMC3069207 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature