MAHRP-1, a novel Plasmodium falciparum histidine-rich protein, binds ferriprotoporphyrin IX and localizes to the Maurer's clefts.
Using a stage-specific cDNA library from Plasmodium falciparum we have identified a gene coding for a novel histidine-rich protein (MAHRP-1). The gene is exclusively transcribed during early erythrocyte stages and codes for a small transmembrane protein. The C-terminal region contains a polymorphic stretch of histidine-rich repeats. Fluorescence microscopy studies using polyclonal mouse sera revealed that MAHRP-1 is located at the Maurer's clefts, which represent parasite-induced structures within the cytosol of infected erythrocytes. Biochemical studies showed that recombinant MAHRP-1 binds the toxic hemoglobin degradation product, ferriprotoporphyrin (FP) with a submicromolar dissociation constant and a stoichiometry determined by the number of DHGH motifs. The bound FP has increased peroxidase-like activity and is 10-fold more susceptible to H2O2-induced degradation compared with unbound FP. These properties of MAHRP-1 suggest it may play a protective role against oxidative stress, and its location at the Maurer's clefts suggests a function in promoting the correct trafficking of exported proteins, such as P. falciparum erythrocyte membrane protein-1.
Spycher
Cornelia
C
Department of Medical Parasitology and Infection Biology, Swiss Tropical Institute, Socinstrasse 51, CH-4051 Basel, Switzerland.
Klonis
Nectarios
N
Spielmann
Tobias
T
Kump
Erwin
E
Steiger
Sylvia
S
Tilley
Leann
L
Beck
Hans-Peter
HP
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017931:DNA Primers; D016054:DNA, Protozoan / Q000235:genetics; D004912:Erythrocytes / Q000469:parasitology*; D006427:Hemin / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D008969:Molecular Sequence Data; D015388:Organelles / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000737:chemistry / Q000166:cytology / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D015183:Restriction Mapping; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012995:Solubility; D013552:Swine
D002352:Carrier Proteins; D017931:DNA Primers; D016054:DNA, Protozoan; C478484:MAHRP-1 protein, Plasmodium falciparum; D008565:Membrane Proteins; D015800:Protozoan Proteins; D011994:Recombinant Proteins; D006427:Hemin