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

• Published in: Blood Vol. 98; no. 8; pp. 2555 - 2562
• Main Authors: Loyevsky, Mark, LaVaute, Timothy, Allerson, Charles R., Stearman, Robert, Kassim, Olakunle O., Cooperman, Sharon, Gordeuk, Victor R., Rouault, Tracey A.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.10.2001; The Americain Society of Hematology
• Subjects: Aconitate Hydratase - metabolism; Amino Acid Sequence; Animals; Base Sequence; Binding Sites; Biological and medical sciences; Blotting, Western; Cloning, Molecular; Consensus Sequence; Deferoxamine - pharmacology; DNA Primers; Erythrocytes - parasitology; Fluorescent Antibody Technique, Indirect; Hemoglobins - metabolism; Human protozoal diseases; Humans; Infectious diseases; Iron - metabolism; Iron Regulatory Protein 1; Iron-Regulatory Proteins; Iron-Sulfur Proteins - genetics; Iron-Sulfur Proteins - metabolism; Malaria; Mammals; Medical sciences; Molecular Sequence Data; Parasitic diseases; Plasmodium falciparum - drug effects; Plasmodium falciparum - physiology; Protozoal diseases; Protozoan Proteins - metabolism; Recombinant Proteins - metabolism; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; Sequence Alignment; Sequence Homology, Amino Acid; Transcription, Genetic; Human; Iron regulatory protein; Protozoa; Apicomplexa; Protozoal disease; Malaria; Pathogenesis; Red blood cell; Iron; Parasitosis; Metabolism; Infection; Plasmodium falciparum; Binding protein; Infected cell
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V98.8.2555

This study cloned and sequenced the complementary DNA (cDNA) encoding of a putative malarial iron responsive element-binding protein (PfIRPa) and confirmed its identity to the previously identified iron-regulatory protein (IRP)–like cDNA from Plasmodium falciparum. Sequence alignment showed that the plasmodial sequence has 47% identity with human IRP1. Hemoglobin-free lysates obtained from erythrocyte-stage P falciparum contain a protein that binds a consensus mammalian iron-responsive element (IRE), indicating that a protein(s) with iron-regulatory activity was present in the lysates. IRE-binding activity was found to be iron regulated in the electrophoretic mobility shift assays. Western blot analysis showed a 2-fold increase in the level of PfIRPa in the desferrioxamine-treated cultures versus control or iron-supplemented cells. Malarial IRP was detected by anti-PfIRPa antibody in the IRE-protein complex fromP falciparum lysates. Immunofluorescence studies confirmed the presence of PfIRPa in the infected red blood cells. These findings 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 iron-dependently regulated.