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

Virginia Lorenz; Yanina Ditamo; Romina B Cejas; Maria E Carrizo; Eric P Bennett; Henrik Clausen; Gustavo A Nores; Fernando J Irazoqui

doi:10.1074/jbc.m116.740795

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

Virginia Lorenz, Yanina Ditamo, Romina B Cejas, Maria E Carrizo, Eric P Bennett, Henrik Clausen, Gustavo A Nores, Fernando J Irazoqui

7 Citations (Scopus)

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.

Original language	English
Journal	Journal of Biological Chemistry
Volume	291
Pages (from-to)	25339-25350
Number of pages	12
ISSN	0021-9258
DOIs	https://doi.org/10.1074/jbc.m116.740795
Publication status	Published - 2 Dec 2016

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@article{634fedef1dfd4eaf9c636380f3cc1398,

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.",

author = "Virginia Lorenz and Yanina Ditamo and Cejas, {Romina B} and Carrizo, {Maria E} and Bennett, {Eric P} and Henrik Clausen and Nores, {Gustavo A} and Irazoqui, {Fernando J}",

note = "Copyright {\textcopyright} 2016, The American Society for Biochemistry and Molecular Biology.",

year = "2016",

month = dec,

day = "2",

doi = "10.1074/jbc.m116.740795",

language = "English",

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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

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 -

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

Abstract

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