Distinct donor and acceptor specificities of Trypanosoma brucei oligosaccharyltransferases

Izquierdo, Luis, Schulz, Benjamin L., Rodrigues, João A., Güther, Maria Lucia S., Procter, James B., Barton, Geoffrey J., Aebi, Markus and Ferguson, Michael A. J. (2009) Distinct donor and acceptor specificities of Trypanosoma brucei oligosaccharyltransferases. EMBO Journal, 28 17: 2650-2661. doi:10.1038/emboj.2009.203

Author Izquierdo, Luis
Schulz, Benjamin L.
Rodrigues, João A.
Güther, Maria Lucia S.
Procter, James B.
Barton, Geoffrey J.
Aebi, Markus
Ferguson, Michael A. J.
Title Distinct donor and acceptor specificities of Trypanosoma brucei oligosaccharyltransferases
Journal name EMBO Journal   Check publisher's open access policy
ISSN 0261-4189
Publication date 2009-09-02
Sub-type Article (original research)
DOI 10.1038/emboj.2009.203
Volume 28
Issue 17
Start page 2650
End page 2661
Total pages 12
Place of publication United Kingdom, Germany
Publisher Nature Publishing Group
Language eng
Subject 0601 Biochemistry and Cell Biology
Formatted abstract
Asparagine-linked glycosylation is catalysed by oligosaccharyltransferase (OTase). In Trypanosoma brucei OTase activity is catalysed by single-subunit enzymes encoded by three paralogous genes of which TbSTT3B and TbSTT3C can complement a yeast Δstt3 mutant. The two enzymes have overlapping but distinct peptide acceptor specificities, with TbSTT3C displaying an enhanced ability to glycosylate sites flanked by acidic residues. TbSTT3A and TbSTT3B, but not TbSTT3C, are transcribed in the bloodstream and procyclic life cycle stages of T. brucei. Selective knockdown and analysis of parasite protein N-glycosylation showed that TbSTT3A selectively transfers biantennary Man5GlcNAc2 to specific glycosylation sites whereas TbSTT3B selectively transfers triantennary Man9GlcNAc2 to others. Analysis of T. brucei glycosylation site occupancy showed that TbSTT3A and TbSTT3B glycosylate sites in acidic to neutral and neutral to basic regions of polypeptide, respectively. This embodiment of distinct specificities in single-subunit OTases may have implications for recombinant glycoprotein engineering. TbSTT3A and TbSTT3B could be knocked down individually, but not collectively, in tissue culture. However, both were independently essential for parasite growth in mice, suggesting that inhibiting protein N-glycosylation could have therapeutic potential against trypanosomiasis.
Keyword glycosylation
Q-Index Code C1
Q-Index Status Provisional Code

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Chemistry and Molecular Biosciences
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Created: Thu, 23 Sep 2010, 08:55:53 EST by Laura McTaggart on behalf of Faculty of Science