Artículo
Functional control of polypeptide GalNAc-transferase 3 through an acetylation site in the C-terminal lectin domain
Lorenz, Virginia
; Cejas, Romina Beatríz
; Bennett, Eric P.; Nores, Gustavo Alejandro
; Irazoqui, Fernando Jose
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Fecha de publicación:
01/2017
Editorial:
De Gruyter
Revista:
Biological Chemistry
ISSN:
1431-6730
e-ISSN:
1437-4315
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
O-GalNAc glycans are important structures in cellular homeostasis. Their biosynthesis is initiated by members of the polypeptide GalNAc-transferase (ppGalNAc-T) enzyme family. Mutations in ppGalNAc-T3 isoform cause diseases (congenital disorders of glycosylation) in humans. The K626 residue located in the C-terminal β-trefoil fold of ppGalNAc-T3 was predicted to be a site with high likelihood of acetylation by CBP/p300 acetyltransferase. We used a site-directed mutagenesis approach to evaluate the role of this acetylation site in biological properties of the enzyme. Two K626 mutants of ppGalNAc-T3 (T3K626Q and T3K626A) had GalNAc-T activities lower than that of wild-type enzyme. Direct and competitive interaction assays revealed that GalNAc recognition by the lectin domain was altered in the mutants. The presence of GlcNAc glycosides affected the interaction of the three enzymes with mucin-derived peptides. In GalNAc-T activity assays, the presence of GlcNAc glycosides significantly inhibited activity of the mutant (T3K626Q) that mimicked acetylation. Our findings, taken together, reveal the crucial role of the K626 residue in the C-terminal β-trefoil fold in biological properties of human ppGalNAc-T3. We propose that acetylated residues on ppGalNAc-T3 function as control points for enzyme activity, and high level of GlcNAc glycosides promote a synergistic regulatory mechanism, leading to a metabolically disordered state.
Palabras clave:
Glycosyltransferase
,
K626 Site
,
Lectin Domain
,
O-Galnac Glycans
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Articulos(CIQUIBIC)
Articulos de CENTRO DE INVEST.EN QCA.BIOL.DE CORDOBA (P)
Articulos de CENTRO DE INVEST.EN QCA.BIOL.DE CORDOBA (P)
Citación
Lorenz, Virginia; Cejas, Romina Beatríz; Bennett, Eric P.; Nores, Gustavo Alejandro; Irazoqui, Fernando Jose; Functional control of polypeptide GalNAc-transferase 3 through an acetylation site in the C-terminal lectin domain; De Gruyter; Biological Chemistry; 398; 11; 1-2017; 1237-1246
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