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Originally published In Press as doi:10.1074/jbc.M305851200 on June 18, 2003
J. Biol. Chem., Vol. 278, Issue 37, 35373-35383, September 12, 2003
MAHRP-1, a Novel Plasmodium falciparum Histidine-rich Protein, Binds Ferriprotoporphyrin IX and Localizes to the Maurer's Clefts*
Cornelia Spycher ,
Nectarios Klonis ,
Tobias Spielmann ¶,
Erwin Kump ||,
Sylvia Steiger ,
Leann Tilley and
Hans-Peter Beck **
From the
Department of Medical Parasitology and
Infection Biology, Swiss Tropical Institute, Socinstrasse 51, CH-4051 Basel,
Switzerland and Department of Biochemistry, La
Trobe University, Bundoora, 3086 Victoria, Australia
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.
Received for publication, June 4, 2003
, and in revised form, June 17, 2003.
The nucleotide sequence(s) reported in this paper has been submitted to
the GenBankTM/EBI Data Bank with accession number(s)
AY355312AY355318.
* This work was supported by the National Health and Medical Research
Council, Australia, and Swiss National Science Foundation Grant 31-59064.99.
The costs of publication of this article were defrayed in part by the payment
of page charges. This article must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section 1734
solely to indicate this fact.
¶ Present address: Queensland Institute of Medical Research, Brisbane, P. O.
Royal Brisbane Hospital, Brisbane, QLD 4029, Australia.
|| Present address: Institute of Medical Microbiology, Petersplatz 10, CH-4003
Basel, Switzerland.
**
To whom correspondence should be addressed. Tel.: 41-61-284-81-16; Fax:
41-61-271-86-54; E-mail:
Hans-Peter.Beck{at}unibas.ch.

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Copyright © 2003 by the American Society for Biochemistry and Molecular Biology.
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