title: Neutralization of toxic heme by Plasmodium falciparum histidine-rich protein 2.
abstract: Plasmodium falciparum histidine-rich protein 2 (PfHRP2) has been suggested to be an initiator of the polymerization of heme, which is produced as by-product on the digestion of hemoglobin, and a promoter of the H(2)O(2)-induced degradation of heme in food vacuoles of the malarial parasite. In this work, we have designed PfHRP2 model peptides, R18 and R27 (18 and 27 residues, respectively), and used them for optical and electron spin resonance spectroscopic measurements to confirm that the axial ligands of the heme-PfHRP2 complex are the nitrogenous donors derived from the imidazole moieties of histidine residues of PfHRP2. In addition, we revealed that the affinities of R18 and R27 for heme (K(d) = 2.21 x 10(-6) M and 0.71 x 10(-6) M, respectively) might be as high as that of PfHRP2 (K(d) = 0.94 x 10(-6) M). The R27 peptide can remove heme from membrane-intercalated heme and inhibit heme-induced hemolysis. Therefore, we suggest another function of PfHRP2: it may play an important role in the neutralization of toxic heme in the parasite cytoplasm and infected erythrocytes by removing heme from heme-bound membranes or reducing heme-induced hemolysis.
authors.affiliation: Department of Applied Biology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan.
authors.forename: Nguyen Tien
authors.initials: NT
authors.lastname: Huy
authors.forename: Satoshi
authors.initials: S
authors.lastname: Serada
authors.forename: Dai Thi Xuan
authors.initials: DT
authors.lastname: Trang
authors.forename: Ryo
authors.initials: R
authors.lastname: Takano
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Kondo
authors.forename: Kenji
authors.initials: K
authors.lastname: Kanaori
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Tajima
authors.forename: Saburo
authors.initials: S
authors.lastname: Hara
authors.forename: Kaeko
authors.initials: K
authors.lastname: Kamei
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004578:Electron Spin Resonance Spectroscopy; D004910:Erythrocyte Membrane / Q000737:chemistry / Q000378:metabolism; D005290:Ferric Compounds / Q000737:chemistry; D006418:Heme / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D020449:Repetitive Sequences, Amino Acid; D013053:Spectrophotometry / Q000379:methods; D017186:Titrimetry; D000099053:Histidine-Rich Glycoprotein
chemical_list: D005290:Ferric Compounds; D009842:Oligopeptides; D011506:Proteins; D000099053:Histidine-Rich Glycoprotein; D006418:Heme