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J Biol Chem, Vol. 273, Issue 22, 13509-13523, May 29, 1998
Stage-specific Proteophosphoglycan from Leishmania
mexicana Amastigotes
STRUCTURAL CHARACTERIZATION OF NOVEL MONO-, DI-, AND
TRIPHOSPHORYLATED PHOSPHODIESTER-LINKED OLIGOSACCHARIDES
Thomas
Ilg §,
David
Craik ,
Graeme
Currie ,
Gerd
Multhaup**, and
Antony
Bacic
From the Plant Cell Biology Research Centre, School
of Botany, University of Melbourne, Victoria 3052, Australia, the
§ Walter and Eliza Hall Institute of Medical Research,
P. O. Royal Melbourne Hospital, Victoria 3050, Australia, the
Centre for Drug Design and Development, University of
Queensland, Brisbane, Queensland 4072, Australia, and the ** Centre for
Molecular Biology, Heidelberg, Federal Republic of Germany
Intracellular amastigotes of the
protozoan parasite Leishmania mexicana secrete a
macromolecular proteophosphoglycan (aPPG) into the phagolysosome of
their host cell, the mammalian macrophage. The structures of aPPG
glycans were analyzed by a combination of high pH anion exchange high
pressure liquid chromatography, gas chromatography-mass spectrometry,
enzymatic digestions, electrospray-mass spectrometry as well as
1H and 31P NMR spectroscopy. Some glycans are
identical to oligosaccharides known from Leishmania
mexicana promastigote lipophosphoglycan and secreted acid
phosphatase. However, the majority of the aPPG glycans represent
amastigote stage-specific and novel structures. These include neutral
glycans ([Glc 1-3]1-2Gal 1-4Man,
Gal 1-3Gal 1-4Man, Gal 1-3Glc 1-3Gal 1-4Man), several
monophosphorylated glycans containing the conserved phosphodisaccharide
backbone (R-3-[PO4-6-Gal] 1-4Man) but carrying
stage-specific modifications (R = Gal 1-,
[Glc 1-3]1-2Glc 1-), and monophosphorylated aPPG
tri- and tetrasaccharides that are uniquely phosphorylated on the
terminal hexose (PO4-6-Glc 1-3Gal 1-4Man, PO4-6-Glc 1-3Glc 1-3Gal 1-4Man,
PO4-6-Gal 1-3Glc 1-3Gal 1-4Man). In addition aPPG
contains highly unusual di- and triphosphorylated glycans whose major
species are
PO4-6-Glc 1-3Glc 1-3[PO4-6-Gal] 1-4Man, PO4-6-Gal 1-3Glc 1-3[PO4-6-Gal] 1-4Man,
PO4-6-Gal 1-3Glc 1-3Glc 1-3[PO4-6-Gal] 1-4Man, PO4-6-Glc 1-3[PO4-6-Glc] 1-3[PO4-6-Gal] 1-4Man,
PO4-6-Gal 1-3[PO4-6-Glc] 1-3Glc 1-3[PO4-6-Gal] 1-4Man, and
PO4-6-Glc 1-3[PO4-6-Glc] 1-3Glc 1-3[PO4-6-Gal] 1-4Man.
These glycans are linked together by the conserved phosphodiester
R-Man 1-PO4-6-Gal-R or the novel
phosphodiester R-Man 1-PO4-6-Glc-R and are connected to
Ser(P) of the protein backbone most likely via the linkage R-Man 1-PO4-Ser. The variety of stage-specific glycan
structures in Leishmania mexicana aPPG suggests the
presence of developmentally regulated amastigote
glycosyltransferases which may be potential anti-parasite drug
targets.
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 1998 by the American Society for Biochemistry and Molecular Biology.
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