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

TY - JOUR

T1 - Extrinsic functions of lectin domains in O-N-acetylgalactosamine glycan biosynthesis

AU - Lorenz, Virginia

AU - Ditamo, Yanina

AU - Cejas, Romina B

AU - Carrizo, Maria E

AU - Bennett, Eric P

AU - Clausen, Henrik

AU - Nores, Gustavo A

AU - Irazoqui, Fernando J

N1 - Copyright © 2016, The American Society for Biochemistry and Molecular Biology.

PY - 2016/12/2

Y1 - 2016/12/2

N2 - 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.

AB - 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.

U2 - 10.1074/jbc.m116.740795

DO - 10.1074/jbc.m116.740795

M3 - Journal article

C2 - 27738109

SN - 0021-9258

VL - 291

SP - 25339

EP - 25350

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

ER -