Plasmodium Hemozoin Formation Mediated by Histidine-Rich Proteins

The digestive vacuole of Plasmodium falciparum is the site of hemoglobin degradation, heme polymerization into crystalline hemozoin, and antimalarial drug accumulation. Antibodies identified histidine-rich protein II (HRP II) in purified digestive vacuoles. Recombinant or native HRP II promoted the formation of hemozoin, and chloroquine inhibited the reaction. The related HRP III also polymerized heme, and an additional HRP was identified in vacuoles. It is proposed that after secretion by the parasite into the host erythrocyte cytosol, HRPs are brought into the acidic digestive vacuole along with hemoglobin. After hemoglobin proteolysis, HRPs bind the liberated heme and mediate hemozoin formation.

[1]  D. Goldberg,et al.  The plasmodium digestive vacuole: metabolic headquarters and choice drug target. , 1995, Parasitology today.

[2]  Theodore F. Taraschi,et al.  Cloning the P. falciparum gene encoding PfEMP1, a malarial variant antigen and adherence receptor on the surface of parasitized human erythrocytes , 1995, Cell.

[3]  Joseph D. Smith,et al.  Switches in expression of plasmodium falciparum var genes correlate with changes in antigenic and cytoadherent phenotypes of infected erythrocytes , 1995, Cell.

[4]  X. Su,et al.  The large diverse gene family var encodes proteins involved in cytoadherence and antigenic variation of plasmodium falciparum-infected erythrocytes , 1995, Cell.

[5]  H. Matile,et al.  Malarial haemozoin/β-haematin supports haem polymerization in the absence of protein , 1995, Nature.

[6]  T. Egan,et al.  Quinoline anti‐malarial drugs inhibit spontaneous formation of β‐haematin (malaria pigment) , 1994 .

[7]  P. Rathod,et al.  Plasmodium falciparum S-adenosylhomocysteine hydrolase. cDNA identification, predicted protein sequence, and expression in Escherichia coli. , 1994, The Journal of biological chemistry.

[8]  I. Gluzman,et al.  Order and specificity of the Plasmodium falciparum hemoglobin degradation pathway. , 1994, The Journal of clinical investigation.

[9]  C. Shiff,et al.  The rapid manual ParaSight-F test. A new diagnostic tool for Plasmodium falciparum infection. , 1993, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[10]  D. Goldberg,et al.  Hemoglobin degradation in Plasmodium-infected red blood cells. , 1993, Seminars in cell biology.

[11]  H. Bujard,et al.  Thrombospondin related anonymous protein (TRAP) of Plasmodium falciparum binds specifically to sulfated glycoconjugates and to HepG2 hepatoma cells suggesting a role for this molecule in sporozoite invasion of hepatocytes. , 1993, The EMBO journal.

[12]  H. Ginsburg,et al.  Impairment of macrophage functions after ingestion of Plasmodium falciparum-infected erythrocytes or isolated malarial pigment [published erratum appears in J Exp Med 1993 Mar 1;177(3):following 873] , 1992, The Journal of experimental medicine.

[13]  T. Wellems,et al.  An RFLP map of the Plasmodium falciparum genome, recombination rates and favored linkage groups in a genetic cross. , 1992, Molecular and biochemical parasitology.

[14]  A. Cerami,et al.  Inhibition by chloroquine of a novel haem polymerase enzyme activity in malaria trophozoites , 1992, Nature.

[15]  C. B. Evans,et al.  Identification of Plasmodium falciparum histidine-rich protein 2 in the plasma of humans with malaria , 1991, Journal of clinical microbiology.

[16]  D. Galatis,et al.  A P-glycoprotein homologue of Plasmodium falciparum is localized on the digestive vacuole , 1991, The Journal of cell biology.

[17]  T. Wellems,et al.  Genetic mapping of the chloroquine-resistance locus on Plasmodium falciparum chromosome 7. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[18]  D. Goldberg,et al.  An iron-carboxylate bond links the heme units of malaria pigment. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[19]  D. Goldberg,et al.  Hemoglobin degradation in the malaria parasite Plasmodium falciparum: an ordered process in a unique organelle. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[20]  T. Wellems,et al.  Purification and partial characterization of an unusual protein of Plasmodium falciparum: histidine-rich protein II. , 1989, Molecular and biochemical parasitology.

[21]  J. Ravetch,et al.  Large deletions result from breakage and healing of P. falciparum chromosomes , 1988, Cell.

[22]  Y. Shimonishi,et al.  Interaction of heme with a synthetic peptide mimicking the putative heme-binding site of histidine-rich glycoprotein. , 1987, Biochemical and biophysical research communications.

[23]  E. Rock,et al.  Comparative analysis of the Plasmodium falciparum histidine-rich proteins HRP-I, HRP-II and HRP-III in malaria parasites of diverse origin , 1987, Parasitology.

[24]  F. Galibert,et al.  Cloning and sequencing of Plasmodium falciparum DNA fragments containing repetitive regions potentially coding for histidine-rich proteins: identification of two overlapping reading frames. , 1987, Biochemical and biophysical research communications.

[25]  T. Wellems,et al.  Secretion of a malarial histidine-rich protein (Pf HRP II) from Plasmodium falciparum-infected erythrocytes , 1986, The Journal of cell biology.

[26]  T. Wellems,et al.  Homologous genes encode two distinct histidine-rich proteins in a cloned isolate of Plasmodium falciparum. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[27]  E. Davie,et al.  Amino acid sequence of human histidine-rich glycoprotein derived from the nucleotide sequence of its cDNA. , 1986, Biochemistry.

[28]  D. V. Vander Jagt,et al.  Characterization of a hemoglobin-degrading, low molecular weight protease from Plasmodium falciparum. , 1986, Molecular and biochemical parasitology.

[29]  R. Coppel,et al.  Sequence of a cDNA encoding a small polymorphic histidine- and alanine-rich protein from Plasmodium falciparum. , 1985, Nucleic acids research.

[30]  W. T. Morgan,et al.  Preferred heme binding sites of histidine-rich glycoprotein. , 1985, Biochemistry.

[31]  W. T. Morgan,et al.  The histidine-rich glycoprotein of serum has a domain rich in histidine, proline, and glycine that binds heme and metals. , 1985, Biochemistry.

[32]  M. Pfaller,et al.  Lysis of Plasmodium falciparum by ferriprotoporphyrin IX and a chloroquine-ferriprotoporphyrin IX complex , 1982, Antimicrobial Agents and Chemotherapy.

[33]  C. D. Fitch,et al.  Hemin lyses malaria parasites. , 1981, Science.

[34]  A. Chou,et al.  Ferriprotoporphyrin IX fulfills the criteria for identification as the chloroquine receptor of malaria parasites. , 1980, Biochemistry.

[35]  W. Trager,et al.  Human malaria parasites in continuous culture. , 1976, Science.

[36]  U. K. Laemmli,et al.  Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 , 1970, Nature.

[37]  A. Chou,et al.  Heme polymerase: modulation by chloroquine treatment of a rodent malaria. , 1992, Life sciences.

[38]  F. Studier,et al.  Use of T7 RNA polymerase to direct expression of cloned genes. , 1990, Methods in enzymology.

[39]  D. Goldberg.  Hemoglobin degradation in the malaria parasite : an ordered process in a unique organelle , 1990 .