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J. Biol. Chem., Vol. 277, Issue 25, 22353-22360, June 21, 2002
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From the The free-living amoeboflagellate and potential
human pathogen Naegleria fowleri causes the often fatal
disease primary amoebic meningoencephalitis. The molecular repertoire
responsible for the cytolytic and tissue-destructive activity of this
amoeboid protozoon is largely unknown. We isolated two
pore-forming polypeptides from extracts of highly virulent
trophozoites of N. fowleri by measuring their
membrane-permeabilizing activity. N-terminal sequencing and subsequent
molecular cloning yielded the complete primary structures and revealed
that the two polypeptides are isoforms. Both polypeptides share similar
structural properties with antimicrobial and cytolytic polypeptides of
the protozoon Entamoeba histolytica (amoebapores) and of
cytotoxic natural killer (NK) and T cells of human (granulysin)
and pig (NK-lysin), all characterized by a structure of amphipathic
The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) AF154046, AF154047, AF196308, and AF196309.
Pore-forming Polypeptides of the Pathogenic Protozoon
Naegleria fowleri*
§,¶,,
,§
Bernhard Nocht Institute for
Tropical Medicine, Bernhard-Nocht-Strasse 74, 20359 Hamburg, Germany,
the § Molecular Parasitology Group, Research Center for
Infectious Diseases, Röntgenring 11, 97070 Würzburg,
Germany, and the ** Department of Microbiology and
Immunology, Virginia Commonwealth University, Medical College of
Virginia, Richmond, Virginia 23298
-helices and an invariant framework of cysteine residues involved in
disulfide bonds. In contrast to the aforementioned proteins, the
Naegleria polypeptides both are processed from large
precursor molecules containing additional isoforms of substantial
sequence divergence. Moreover, biochemical characterization of the
isolated polypeptides in combination with mass determination showed
that they are N-glycosylated and variably processed at the
C terminus. The biological activity of the purified polypeptides of
Naegleria was examined toward human cells and bacteria, and
it was found that these factors, named naegleriapores, are active
against both types of target cells, which is in good agreement with
their proposed biological role as a broad-spectrum effector molecule.
*
This work was supported by the Deutsche
Forschungsgemeinschaft by Grant LE 1075/2-3 and by a Heisenberg
fellowship (to M. L.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Present address: Megamedics, Hafenstrasse 32, 22880 Wedel, Germany.
To whom correspondence should be addressed. Tel.:
49-931-31-2151; Fax: 49-931-31-2578; E-mail:
matthias.leippe@mail.uni-wuerzburg.de.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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