N-glycosylations of human a1,3-fucosyltransferase IX are required for full enzyme activity

Authors:
Seelhorst K1, Stacke C, Ziegelmüller P, Hahn U.
In:
Source: Glycobiology
Publication Date: (2013)
Issue: 23(5): 559-67
Research Area:
Basic Research
Cells used in publication:
Sf9
Species: spodoptera frugiperda (army fall worm)
Tissue Origin: ovarian
Culture Media:
Experiment


Abstract

Human a1,3-fucosyltransferase IX catalyzes the transfer of l-fucose from guanosine diphosphate-ß-L-fucose to N-acetyllactosamine, generating a Lewis X epitope, and is thereby involved in the synthesis of fucosylated cell surface glycoconjugates. It contains three putative N-glycosylation sites (Asn62, Asn101 and Asn153). The current study considers the functional role of these potential N-glycosylations within the enzyme. We produced truncated variants of human fucosyltransferase IX containing the soluble extracellular catalytic domain. To analyze the relevance of each N-glycosylation site, several genomic mutant DNAs encoding a glutamine (Gln/Q) instead of the asparagine residue were created prosperously using site-directed mutagenesis and subsequently expressed in Spodoptera frugiperda cells applying a baculovirus expression system. After production and purification of these variants of human FucT IX, the wild-type (wt) enzyme and the variants were characterized regarding their activity and kinetic properties. The variants showed lower activity than the wt FucT, whereas the individual N-glycosylation sites had different effects on the enzyme activity and kinetic parameters. While the single variant N62Q still showed ~60% of wt activity and N101Q retained ~30% activity, replacement of Asn153 by glutamine led to an almost complete loss of enzymatic activity. The same could be observed for variants missing two or more putative N-glycosylation sites, which indicated the importance of N-glycosylation for enzyme stability and activity.