Extrinsic functions of lectin domains in O-N-acetylgalactosamine glycan biosynthesis

LORENS V; DITAMO Y; CEJAS RB; CARRIZO ME; BENNET EP; KLAUSEN H; NORES GA; IRAZOQUI FJ

JOURNAL OF BIOLOGICAL CHEMISTRY

AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

Lugar: Bethesda, Maryland; Año: 2016 vol. 291 p. 25339 - 25339

0021-9258

lycan biosynthesis occurs mainly in Golgi. Molecular organizationand functional regulation of this process are not wellunderstood. We evaluated the extrinsic effect of lectin domains(_-trefoil fold) of polypeptide GalNAc-transferases (ppGalNAc-Ts) on catalytic activity of glycosyltransferases during OGalNAcglycan biosynthesis. The presence of lectin domainT3lec or T4lec during ppGalNAc-T2 and ppGalNAc-T3 catalyticreaction had a clear inhibitory effect on GalNAc-T activity.Interaction of T3lec or T4lec with ppGalNAc-T2 catalytic domainwas not mediated by carbohydrate. T3lec, but not T2lec and T4lec,had a clear activating effect on Drosophila melanogaster core 1galactosyltransferase enzyme activity and a predominant inhibitoryeffect on in vivo human core 1 glycan biosynthesis. The regulatoryrole of the_-trefoil fold of ppGalNAc-Ts in enzymatic activityof glycosyltransferases involved in the O-glycan biosynthesispathway, described here for the first time, helps clarify the mechanismof bi