Assembly of B4GALT1/ST6GAL1 heteromers in ...
Type de document :
Article dans une revue scientifique
DOI :
PMID :
URL permanente :
Titre :
Assembly of B4GALT1/ST6GAL1 heteromers in the Golgi membranes involves lateral interactions via highly charged surface domains.
Auteur(s) :
Khoder-Agha, Fawzi [Auteur]
Harrus, Deborah [Auteur]
Brysbaert, Guillaume [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Lensink, Marc [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Harduin Lepers, Anne [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Glumoff, Tuomo [Auteur]
Kellokumpu, Sakari [Auteur]
Harrus, Deborah [Auteur]
Brysbaert, Guillaume [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Lensink, Marc [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Harduin Lepers, Anne [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Glumoff, Tuomo [Auteur]
Kellokumpu, Sakari [Auteur]
Titre de la revue :
THE JOURNAL OF BIOLOGICAL CHEMISTRY
Nom court de la revue :
J. Biol. Chem.
Numéro :
294
Pagination :
14383-14393
Éditeur :
American Society for Biochemistry & Molecular Biology (ASBMB)
Date de publication :
2019-09-27
ISSN :
1083-351X
Mot(s)-clé(s) en anglais :
Animals
Antigens, CD
Binding Sites
CHO Cells
COS Cells
Chlorocebus aethiops
Cricetinae
Cricetulus
Fluorescence Resonance Energy Transfer
Galactosyltransferases
Golgi Apparatus
Molecular Docking Simulation
Protein Multimerization
Sialyltransferases
Static Electricity
galactosyltransferase
glycosyltransferase
molecular interplay
protein complex
protein–protein interaction
β-galactoside α-2,6-sialyltransferase 1 (ST6GAL1)
Antigens, CD
Binding Sites
CHO Cells
COS Cells
Chlorocebus aethiops
Cricetinae
Cricetulus
Fluorescence Resonance Energy Transfer
Galactosyltransferases
Golgi Apparatus
Molecular Docking Simulation
Protein Multimerization
Sialyltransferases
Static Electricity
galactosyltransferase
glycosyltransferase
molecular interplay
protein complex
protein–protein interaction
β-galactoside α-2,6-sialyltransferase 1 (ST6GAL1)
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Chimie/Chimie théorique et/ou physique
Chimie/Chimie théorique et/ou physique
Résumé en anglais : [en]
β-1,4-Galactosyltransferase 1 (B4GALT1) and ST6 β-galactoside α-2,6-sialyltransferase 1 (ST6GAL1) catalyze the successive addition of terminal β-1,4-linked galactose and α-2,6-linked sialic acid to glycans. Their exclusive ...
Lire la suite >β-1,4-Galactosyltransferase 1 (B4GALT1) and ST6 β-galactoside α-2,6-sialyltransferase 1 (ST6GAL1) catalyze the successive addition of terminal β-1,4-linked galactose and α-2,6-linked sialic acid to glycans. Their exclusive interaction in the Golgi compartment is a prerequisite for their full catalytic activity, whereas a lack of this interaction is associated with cancers and hypoxia. To date, no structural information exists that shows how glycosyltransferases functionally assemble with each other. Using molecular docking simulations to predict interaction surfaces, along with mutagenesis screens and high-throughput FRET analyses in live cells to validate these predictions, we show here that B4GALT1 and ST6GAL1 interact via highly charged noncatalytic surfaces, leaving the active sites exposed and accessible for donor and acceptor substrate binding. Moreover, we found that the assembly of ST6GAL1 homomers in the endoplasmic reticulum before ST6GAL1 activation in the Golgi utilizes the same noncatalytic surface, whereas B4GALT1 uses its active-site surface for assembly, which silences its catalytic activity. Last, we show that the homomeric and heteromeric B4GALT1/ST6GAL1 complexes can assemble laterally in the Golgi membranes without forming cross-cisternal contacts between enzyme molecules residing in the opposite membranes of each Golgi cisterna. Our results provide detailed mechanistic insights into the regulation of glycosyltransferase interactions, the transitions between B4GALT1 and ST6GAL1 homo- and heteromers in the Golgi, and cooperative B4GALT1/ST6GAL1 function in glycan synthesis.Lire moins >
Lire la suite >β-1,4-Galactosyltransferase 1 (B4GALT1) and ST6 β-galactoside α-2,6-sialyltransferase 1 (ST6GAL1) catalyze the successive addition of terminal β-1,4-linked galactose and α-2,6-linked sialic acid to glycans. Their exclusive interaction in the Golgi compartment is a prerequisite for their full catalytic activity, whereas a lack of this interaction is associated with cancers and hypoxia. To date, no structural information exists that shows how glycosyltransferases functionally assemble with each other. Using molecular docking simulations to predict interaction surfaces, along with mutagenesis screens and high-throughput FRET analyses in live cells to validate these predictions, we show here that B4GALT1 and ST6GAL1 interact via highly charged noncatalytic surfaces, leaving the active sites exposed and accessible for donor and acceptor substrate binding. Moreover, we found that the assembly of ST6GAL1 homomers in the endoplasmic reticulum before ST6GAL1 activation in the Golgi utilizes the same noncatalytic surface, whereas B4GALT1 uses its active-site surface for assembly, which silences its catalytic activity. Last, we show that the homomeric and heteromeric B4GALT1/ST6GAL1 complexes can assemble laterally in the Golgi membranes without forming cross-cisternal contacts between enzyme molecules residing in the opposite membranes of each Golgi cisterna. Our results provide detailed mechanistic insights into the regulation of glycosyltransferase interactions, the transitions between B4GALT1 and ST6GAL1 homo- and heteromers in the Golgi, and cooperative B4GALT1/ST6GAL1 function in glycan synthesis.Lire moins >
Langue :
Anglais
Comité de lecture :
Oui
Audience :
Internationale
Vulgarisation :
Non
Établissement(s) :
Université de Lille
CNRS
CNRS
Équipe(s) de recherche :
Computational Molecular Systems Biology
Régulation de la glycosylation terminale
Régulation de la glycosylation terminale
Date de dépôt :
2021-01-04T08:20:57Z
2021-01-04T13:54:04Z
2021-01-14T15:08:56Z
2021-01-04T13:54:04Z
2021-01-14T15:08:56Z
Fichiers
- P19.90 J. Biol. Chem.-2019-Khoder-Agha-14383-93.pdf
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