title: Extrinsic Functions of Lectin Domains in O-N-Acetylgalactosamine Glycan Biosynthesis.
abstract: Glycan biosynthesis occurs mainly in Golgi. Molecular organization and functional regulation of this process are not well understood. We evaluated the extrinsic effect of lectin domains (β-trefoil fold) of polypeptide GalNAc-transferases (ppGalNAc-Ts) on catalytic activity of glycosyltransferases during O-GalNAc glycan biosynthesis. The presence of lectin domain T3lec or T4lec during ppGalNAc-T2 and ppGalNAc-T3 catalytic reaction had a clear inhibitory effect on GalNAc-T activity. Interaction of T3lec or T4lec with ppGalNAc-T2 catalytic domain was not mediated by carbohydrate. T3lec, but not T2lec and T4lec, had a clear activating effect on Drosophila melanogaster core 1 galactosyltransferase enzyme activity and a predominant inhibitory effect on in vivo human core 1 glycan biosynthesis. The regulatory role of the β-trefoil fold of ppGalNAc-Ts in enzymatic activity of glycosyltransferases involved in the O-glycan biosynthesis pathway, described here for the first time, helps clarify the mechanism of biosynthesis of complex biopolymers (such as glycans) that is not template-driven.
authors.affiliation: From the Centro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), and Departamento de Química Biológica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, X5000HUA Córdoba, Argentina and.
authors.forename: Virginia
authors.initials: V
authors.lastname: Lorenz
authors.affiliation: From the Centro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), and Departamento de Química Biológica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, X5000HUA Córdoba, Argentina and.
authors.forename: Yanina
authors.initials: Y
authors.lastname: Ditamo
authors.affiliation: From the Centro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), and Departamento de Química Biológica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, X5000HUA Córdoba, Argentina and.
authors.forename: Romina B
authors.initials: RB
authors.lastname: Cejas
authors.affiliation: From the Centro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), and Departamento de Química Biológica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, X5000HUA Córdoba, Argentina and.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Carrizo
authors.affiliation: Copenhagen Center for Glycomics, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200 Copenhagen, Denmark.
authors.forename: Eric P
authors.initials: EP
authors.lastname: Bennett
authors.affiliation: Copenhagen Center for Glycomics, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200 Copenhagen, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Clausen
authors.affiliation: From the Centro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), and Departamento de Química Biológica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, X5000HUA Córdoba, Argentina and.
authors.forename: Gustavo A
authors.initials: GA
authors.lastname: Nores
authors.affiliation: From the Centro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), and Departamento de Química Biológica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, X5000HUA Córdoba, Argentina and irazoqui@fcq.unc.edu.ar.
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Irazoqui
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D029721:Drosophila Proteins / Q000737:chemistry* / Q000235:genetics; D004331:Drosophila melanogaster; D006367:HeLa Cells; D006801:Humans; D017350:N-Acetylgalactosaminyltransferases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011134:Polysaccharides / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D000072417:Protein Domains; D017510:Protein Folding; D061987:Sf9 Cells; D018411:Spodoptera; D000097763:Polypeptide N-acetylgalactosaminyltransferase
chemical_list: D029721:Drosophila Proteins; D017350:N-Acetylgalactosaminyltransferases; D011134:Polysaccharides; D000097763:Polypeptide N-acetylgalactosaminyltransferase
keywords: glycobiology; glycoprotein biosynthesis; glycosylation inhibitor; lectin; mucin