An acetylation site in lectin domain modulates the biological activity of polypeptide GalNAc-transferase-2
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Natacha Zlocowski
Abstract
Polypeptide GalNAc-transferases (ppGalNAc-Ts) are a family of enzymes that catalyze the initiation of mucin-type O-glycosylation. All ppGalNAc-T family members contain a common (QXW)3 motif, which is present in the R-type lectin group. The acetylation site K521 is part of the QKW motif of β-trefoil in the lectin domain of ppGalNAc-T2. We used a combination of acetylation and site-directed mutagenesis approaches to examine the functional role of K521 in ppGalNAc-T2. Binding assays of non-acetylated and acetylated forms of the mutant ppGalNAc-T2K521Q to various naked and αGalNAc-glycosylated mucin peptides indicated that the degree of interaction of lectin domain with αGalNAc depends on the peptide sequence of mucin. Studies of the inhibitory effect of various carbohydrates on the interactions of ppGalNAc-T2 with MUC1αGalNAc indicate that point K521Q mutation enhance the carbohydrate specificity of lectin domain for αGalNAc. K521Q mutation resulted in an enzyme activity lower than that of the wild-type ppGalNAc-T2, similar to the acetylation of ppGalNAc-T2. We conclude that an acetylation site in the QKW motif of the lectin domain modulates carbohydrate recognition specificity and catalytic activity of ppGalNAc-T2 for partially preglycosylated acceptors and a certain naked peptide. Posttranslational modifications of ppGalNAc-Ts, such as acetylation, may play key roles in modulating the functions of the R-type lectin domains in cellular homeostasis.
©2012 by Walter de Gruyter Berlin Boston
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Artikel in diesem Heft
- Masthead
- Masthead
- Reviews
- Exosomes: the ideal nanovectors for biodelivery
- Biological applications of the electrochemical sensing of nitric oxide: fundamentals and recent developments
- Minireview
- Cerebral cavernous malformation is a vascular disease associated with activated RhoA signaling
- Research Articles/Short Communications
- Protein Structure and Function
- Diversity, abundance, and sex-specific expression of chemosensory proteins in the reproductive organs of the locust Locusta migratoria manilensis
- Structure of the Ca2+-saturated C-terminal domain of scallop troponin C in complex with a troponin I fragment
- An acetylation site in lectin domain modulates the biological activity of polypeptide GalNAc-transferase-2
- Reengineering of subtilisin Carlsberg for oxidative resistance
- New insight into the molecular switch mechanism of human Rho family proteins: shifting a paradigm
- Cell Biology and Signaling
- HbG200-mediated preinduction of heme oxygenase-1 improves bile flow and ameliorates pericentral downregulation of Bsep and Mrp2 following experimental liver ischemia and reperfusion
- Effect of silver nanoparticles on human primary keratinocytes
- Multifunctional silica nanoparticles for optical and magnetic resonance imaging
- Proteolysis
- Activation profiles of human kallikrein-related peptidases by matrix metalloproteinases
