Neutralization of toxic heme by Plasmodium falciparum histidine-rich protein 2.
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.
Huy
Nguyen Tien
NT
Department of Applied Biology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan.
Serada
Satoshi
S
Trang
Dai Thi Xuan
DT
Takano
Ryo
R
Kondo
Yoshiro
Y
Kanaori
Kenji
K
Tajima
Kunihiko
K
Hara
Saburo
S
Kamei
Kaeko
K
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
D005290:Ferric Compounds; D009842:Oligopeptides; D011506:Proteins; D000099053:Histidine-Rich Glycoprotein; D006418:Heme