A gene of the β3-glycosyltransferase family encodes N-acetylglucosaminyltransferase II function in Trypanosoma brucei

Manuela Damerow, Frauke Graalfs, M. Lucia S. Guther, Angela Mehlert, Luis Izquierdo, Michael A. J. Ferguson (Lead / Corresponding author)

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Abstract

The bloodstream form of the human pathogen Trypanosoma brucei expresses oligomannose, paucimannose and complex Nlinked glycans, including some exceptionally large poly-N acetyllactosamine-containing structures. Despite the presence of complex N-glycans in this organism, no homologues of the canonical Nacetylglucosaminyltransferase I or II genes can be found in the T. brucei genome. These genes encode the activities that initiate the elaboration of the Manα1-3 and Manα1-6 arms, respectively, of the conserved trimannosyl-N acetylchitobiosyl core of N-linked glycans. Previously, we identified a highly divergent T. brucei N-acetylglucosaminyltransferase I (TbGnTI) among a set of putative T. brucei glycosyltransferase genes belonging to the β3-glycosyltransferase superfamily (1). Here, we demonstrate that TbGT15, another member of the same β3-glycosyltransferase family, encodes an equally divergent N-acetylglucosaminyltransferase II (TbGnTII) activity. In contrast to multicellular organisms, where GnTII activity is essential, TbGnTII null mutants of T. brucei grow in culture and are still infectious to animals. Characterization of the large poly-Nacetyllactosamine containing N-glycans of the TbGnTII null mutants by methylation linkage analysis suggests that, in wild-type parasites, the Manα1-6 arm of the conserved trimannosyl core may carry predominantly linear poly-Nacetyllactosamine chains whereas the Manα1-3 arm may carry predominantly branched poly-Nacetyllactosamine chains. These results provide further detail on the structure and biosynthesis of complex N-glycans in an important human pathogen and provide a second example of the adaptation by trypanosomes of β3-glycosyltransferase family members to catalyze β1-2 glycosidic linkages.
Original languageEnglish
Pages (from-to)13834-13845
Number of pages12
JournalJournal of Biological Chemistry
Volume291
Issue number26
Early online date4 May 2016
DOIs
Publication statusPublished - 24 Jun 2016

Fingerprint

Glycosyltransferases
Trypanosoma brucei brucei
Polysaccharides
Genes
Pathogens
Methylation
Trypanosomiasis
Biosynthesis
Parasites
Animals
beta-1,3-galactosyl-0-glycosyl-glycoprotein beta-1,3-N-acetylglucosaminyltransferase
Genome

Keywords

  • Glycosyltransferases
  • Glycobiology
  • Trypanosoma brucei
  • Parasite
  • Post translational modification
  • N-acetylglucosamine

Cite this

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title = "A gene of the β3-glycosyltransferase family encodes N-acetylglucosaminyltransferase II function in Trypanosoma brucei",
abstract = "The bloodstream form of the human pathogen Trypanosoma brucei expresses oligomannose, paucimannose and complex Nlinked glycans, including some exceptionally large poly-N acetyllactosamine-containing structures. Despite the presence of complex N-glycans in this organism, no homologues of the canonical Nacetylglucosaminyltransferase I or II genes can be found in the T. brucei genome. These genes encode the activities that initiate the elaboration of the Manα1-3 and Manα1-6 arms, respectively, of the conserved trimannosyl-N acetylchitobiosyl core of N-linked glycans. Previously, we identified a highly divergent T. brucei N-acetylglucosaminyltransferase I (TbGnTI) among a set of putative T. brucei glycosyltransferase genes belonging to the β3-glycosyltransferase superfamily (1). Here, we demonstrate that TbGT15, another member of the same β3-glycosyltransferase family, encodes an equally divergent N-acetylglucosaminyltransferase II (TbGnTII) activity. In contrast to multicellular organisms, where GnTII activity is essential, TbGnTII null mutants of T. brucei grow in culture and are still infectious to animals. Characterization of the large poly-Nacetyllactosamine containing N-glycans of the TbGnTII null mutants by methylation linkage analysis suggests that, in wild-type parasites, the Manα1-6 arm of the conserved trimannosyl core may carry predominantly linear poly-Nacetyllactosamine chains whereas the Manα1-3 arm may carry predominantly branched poly-Nacetyllactosamine chains. These results provide further detail on the structure and biosynthesis of complex N-glycans in an important human pathogen and provide a second example of the adaptation by trypanosomes of β3-glycosyltransferase family members to catalyze β1-2 glycosidic linkages.",
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A gene of the β3-glycosyltransferase family encodes N-acetylglucosaminyltransferase II function in Trypanosoma brucei. / Damerow, Manuela; Graalfs, Frauke; Guther, M. Lucia S.; Mehlert, Angela; Izquierdo, Luis; Ferguson, Michael A. J. (Lead / Corresponding author).

In: Journal of Biological Chemistry, Vol. 291, No. 26, 24.06.2016, p. 13834-13845.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A gene of the β3-glycosyltransferase family encodes N-acetylglucosaminyltransferase II function in Trypanosoma brucei

AU - Damerow, Manuela

AU - Graalfs, Frauke

AU - Guther, M. Lucia S.

AU - Mehlert, Angela

AU - Izquierdo, Luis

AU - Ferguson, Michael A. J.

PY - 2016/6/24

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N2 - The bloodstream form of the human pathogen Trypanosoma brucei expresses oligomannose, paucimannose and complex Nlinked glycans, including some exceptionally large poly-N acetyllactosamine-containing structures. Despite the presence of complex N-glycans in this organism, no homologues of the canonical Nacetylglucosaminyltransferase I or II genes can be found in the T. brucei genome. These genes encode the activities that initiate the elaboration of the Manα1-3 and Manα1-6 arms, respectively, of the conserved trimannosyl-N acetylchitobiosyl core of N-linked glycans. Previously, we identified a highly divergent T. brucei N-acetylglucosaminyltransferase I (TbGnTI) among a set of putative T. brucei glycosyltransferase genes belonging to the β3-glycosyltransferase superfamily (1). Here, we demonstrate that TbGT15, another member of the same β3-glycosyltransferase family, encodes an equally divergent N-acetylglucosaminyltransferase II (TbGnTII) activity. In contrast to multicellular organisms, where GnTII activity is essential, TbGnTII null mutants of T. brucei grow in culture and are still infectious to animals. Characterization of the large poly-Nacetyllactosamine containing N-glycans of the TbGnTII null mutants by methylation linkage analysis suggests that, in wild-type parasites, the Manα1-6 arm of the conserved trimannosyl core may carry predominantly linear poly-Nacetyllactosamine chains whereas the Manα1-3 arm may carry predominantly branched poly-Nacetyllactosamine chains. These results provide further detail on the structure and biosynthesis of complex N-glycans in an important human pathogen and provide a second example of the adaptation by trypanosomes of β3-glycosyltransferase family members to catalyze β1-2 glycosidic linkages.

AB - The bloodstream form of the human pathogen Trypanosoma brucei expresses oligomannose, paucimannose and complex Nlinked glycans, including some exceptionally large poly-N acetyllactosamine-containing structures. Despite the presence of complex N-glycans in this organism, no homologues of the canonical Nacetylglucosaminyltransferase I or II genes can be found in the T. brucei genome. These genes encode the activities that initiate the elaboration of the Manα1-3 and Manα1-6 arms, respectively, of the conserved trimannosyl-N acetylchitobiosyl core of N-linked glycans. Previously, we identified a highly divergent T. brucei N-acetylglucosaminyltransferase I (TbGnTI) among a set of putative T. brucei glycosyltransferase genes belonging to the β3-glycosyltransferase superfamily (1). Here, we demonstrate that TbGT15, another member of the same β3-glycosyltransferase family, encodes an equally divergent N-acetylglucosaminyltransferase II (TbGnTII) activity. In contrast to multicellular organisms, where GnTII activity is essential, TbGnTII null mutants of T. brucei grow in culture and are still infectious to animals. Characterization of the large poly-Nacetyllactosamine containing N-glycans of the TbGnTII null mutants by methylation linkage analysis suggests that, in wild-type parasites, the Manα1-6 arm of the conserved trimannosyl core may carry predominantly linear poly-Nacetyllactosamine chains whereas the Manα1-3 arm may carry predominantly branched poly-Nacetyllactosamine chains. These results provide further detail on the structure and biosynthesis of complex N-glycans in an important human pathogen and provide a second example of the adaptation by trypanosomes of β3-glycosyltransferase family members to catalyze β1-2 glycosidic linkages.

KW - Glycosyltransferases

KW - Glycobiology

KW - Trypanosoma brucei

KW - Parasite

KW - Post translational modification

KW - N-acetylglucosamine

U2 - 10.1074/jbc.M116.733246

DO - 10.1074/jbc.M116.733246

M3 - Article

C2 - 27189951

VL - 291

SP - 13834

EP - 13845

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

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