Artículos de revistas
An acetylation site in lectin domain modulates the biological activity of polypeptide GalNAc-transferase-2
Fecha
2012-12Registro en:
Zlocowski, Natacha; Lorenz, Virginia; Bennett, Eric P.; Clausen, Henrik; Nores, Gustavo Alejandro; et al.; An acetylation site in lectin domain modulates the biological activity of polypeptide GalNAc-transferase-2; De Gruyter; Biological Chemistry; 394; 1; 12-2012; 69-77
1431-6730
CONICET Digital
CONICET
Autor
Zlocowski, Natacha
Lorenz, Virginia
Bennett, Eric P.
Clausen, Henrik
Nores, Gustavo Alejandro
Irazoqui, Fernando Jose
Resumen
Polypeptide GalNAc-transferases (ppGalNAc-Ts) are a family of enzymes that catalyze the initiation of mucintype 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 ppGalNAcT2. 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-T2 K521Q to various naked and α GalNAc-glycosylated mucin peptides indicated that the degree of interaction of lectin domain with α GalNAc depends on the peptide sequence of mucin. Studies of the inhibitory effect of various carbohydrates on the interactions of ppGalNAc-T2 with MUC1 α GalNAc indicate that point K521Q mutation enhance the carbohydrate specificity of lectin domain for α GalNAc. K521Q mutation resulted in an enzyme activity lower than that of the wildtype ppGalNAc-T2, similar to the acetylation of ppGalNAcT2. 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 ppGalNAcTs, such as acetylation, may play key roles in modulating the functions of the R-type lectin domains in cellular homeostasis.