An IRP-like protein from Plasmodium falciparum binds to a mammalian iron-responsive element

This study cloned and sequenced the complementary DNA (cDNA) encoding of a putative malarial iron responsive element-binding protein (PfIRPa) and conf irmed its identity to the previously identified iron-regulatory protein (IR P)-like cDNA from Plasmodium falciparum. Sequence alignment showed that the plasmodial sequence has 47% identity with human IRP1. Hemoglobin-free lysa tes obtained from erythrocyte-stage P falciparum contain a protein that bin ds a consensus mammalian iron-responsive element (IRE), indicating that a p rotein(s) with iron-regulatory activity was present in the lysates. IRE-bin ding activity was found to be iron regulated in the electrophoretic mobilit y shift assays. Western blot analysis showed a 2-fold increase in the level of PflRPa in the desferrioxamine-treated cultures versus control or iron-s upplemented cells. Malarial IRP was detected by anti-PflRPa antibody in the IRE-protein complex from P falciparum lysates. Immunofluorescence studies confirmed the presence of PflRPa in the infected red blood cells. These fin dings demonstrate that erythrocyte P falciparum contains an iron-regulated IRP that binds a mammalian consensus IRE sequence, raising the possibility that the malaria parasite expresses transcripts that contain IREs and are i ron-dependently regulated. (Blood. 2001;98:2555-2562) (C) 2001 by The Ameri can Society of Hematology.