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Identification of the galactosyltransferase of Cryptococcus neoformans involved in the biosynthesis of basidiomycete-type glycosylinositolphosphoceramide

Wohlschlager, Therese ; Buser, Reto ; Skowyra, Michael L. ; Haynes, Brian C. ; Henrissat, Bernard ; Doering, Tamara L. ; Künzler, Markus ; Aebi, Markus

In: Glycobiology, 2013, vol. 23, no. 11, p. 1210-1219

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    Title
    • Identification of the galactosyltransferase of Cryptococcus neoformans involved in the biosynthesis of basidiomycete-type glycosylinositolphosphoceramide
    Author
    • Wohlschlager, Therese. Institute of Microbiology, ETH Zürich, Wolfgang-Pauli-Str. 10, HCI F413, CH-8093 Zürich, Switzerland
    • Buser, Reto. Institute of Microbiology, ETH Zürich, Wolfgang-Pauli-Str. 10, HCI F413, CH-8093 Zürich, Switzerland
    • Skowyra, Michael L.. Department of Molecular Microbiology, Washington University School of Medicine, St Louis, MO 63110, USA
    • Haynes, Brian C.. Department of Molecular Microbiology, Washington University School of Medicine, St Louis, MO 63110, USA
    • Henrissat, Bernard. Laboratoire d'Architecture et de Fonction des Macromolécules Biologiques, UMR6098 CNRS, Universités Aix-Marseille I and II, Case 932, 163 Avenue de Luminy, 13288 Marseille Cedex 9, France
    • Doering, Tamara L.. Department of Molecular Microbiology, Washington University School of Medicine, St Louis, MO 63110, USA
    • Künzler, Markus. Institute of Microbiology, ETH Zürich, Wolfgang-Pauli-Str. 10, HCI F413, CH-8093 Zürich, Switzerland
    • Aebi, Markus. Institute of Microbiology, ETH Zürich, Wolfgang-Pauli-Str. 10, HCI F413, CH-8093 Zürich, Switzerland
    Document Type
    • Postprint
    Language
    • English
    Published in
    • Glycobiology, 2013, vol. 23, no. 11, p. 1210-1219. Oxford University Press
    Other Version
    OAI-PMH Identifier
    • oai:doc.rero.ch:301633
    Summary
    The pathogenic fungus Cryptococcus neoformans synthesizes a complex family of glycosylinositolphosphoceramide (GIPC) structures. These glycosphingolipids (GSLs) consist of mannosylinositolphosphoceramide (MIPC) extended by β1-6-linked galactose, a unique structure that has to date only been identified in basidiomycetes. Further extension by up to five mannose residues and a branching xylose has been described. In this study, we identified and determined the gene structure of the enzyme Ggt1, which catalyzes the transfer of a galactose residue to MIPC. Deletion of the gene in C. neoformans resulted in complete loss of GIPCs containing galactose, a phenotype that could be restored by the episomal expression of Ggt1 in the deletion mutant. The entire annotated open reading frame, encoding a C-terminal GT31 galactosyltransferase domain and a large N-terminal domain of unknown function, was required for complementation. Notably, this gene does not encode a predicted signal sequence or transmembrane domain. The demonstration that Ggt1 is responsible for the transfer of a galactose residue to a GSL thus raises questions regarding the topology of this biosynthetic pathway and the function of the N-terminal domain. Phylogenetic analysis of the GGT1 gene shows conservation in hetero- and homobasidiomycetes but no homologs in ascomycetes or outside of the fungal kingdom