LacdiNAc synthase B4GALNT3 has a unique ...
Type de document :
Article dans une revue scientifique
URL permanente :
Titre :
LacdiNAc synthase B4GALNT3 has a unique PA14 domain and suppresses N-glycan capping
Auteur(s) :
Tokoro, Yuko [Auteur]
Gifu University
Nagae, Masamichi [Auteur]
Osaka University
Nakano, Miyako [Auteur]
Hiroshima University
Harduin-Lepers, Anne [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Kizuka, Yasuhiko [Auteur]
Gifu University
Gifu University
Nagae, Masamichi [Auteur]
Osaka University
Nakano, Miyako [Auteur]
Hiroshima University
Harduin-Lepers, Anne [Auteur]
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Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Kizuka, Yasuhiko [Auteur]
Gifu University
Titre de la revue :
Journal of Biological Chemistry
Nom court de la revue :
Journal of Biological Chemistry
Numéro :
300
Pagination :
107450
Éditeur :
Elsevier BV
Date de publication :
2024-07
ISSN :
0021-9258
Mot(s)-clé(s) en anglais :
B4GALNT3
LacdiNAc
N-linked glycosylation
PA14
glycobiology
glycoprotein biosynthesis
glycosylation
glycosyltransferase
LacdiNAc
N-linked glycosylation
PA14
glycobiology
glycoprotein biosynthesis
glycosylation
glycosyltransferase
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Résumé en anglais : [en]
Structural variation of N-glycans is essential for the regulation of glycoprotein functions. GalNAcβ1-4GlcNAc (LacdiNAc or LDN), a unique subterminal glycan structure synthesized by B4GALNT3 or B4GALNT4, is involved in the ...
Lire la suite >Structural variation of N-glycans is essential for the regulation of glycoprotein functions. GalNAcβ1-4GlcNAc (LacdiNAc or LDN), a unique subterminal glycan structure synthesized by B4GALNT3 or B4GALNT4, is involved in the clearance of N-glycoproteins from the blood and maintenance of cell stemness. Such regulation of glycoprotein functions by LDN is largely different from that by the dominant subterminal structure, N-acetyllactosamine (Galβ1-4GlcNAc, LacNAc). However, the mechanisms by which B4GALNT activity is regulated and how LDN plays different roles from LacNAc remain unclear. Here, we found that B4GALNT3 and four have unique domain organization containing a noncatalytic PA14 domain, which is a putative glycan-binding module. A mutant lacking this domain dramatically decreases the activity toward various substrates, such as N-glycan, O-GalNAc glycan, and glycoproteins, indicating that this domain is essential for enzyme activity and forms part of the catalytic region. In addition, to clarify the mechanism underlying the functional differences between LDN and LacNAc, we examined the effects of LDN on the maturation of N-glycans, focusing on the related glycosyltransferases upstream and downstream of B4GALNT. We revealed that, unlike LacNAc synthesis, prior formation of bisecting GlcNAc in N-glycan almost completely inhibits LDN synthesis by B4GALNT3. Moreover, the presence of LDN negatively impacted the actions of many glycosyltransferases for terminal modifications, including sialylation, fucosylation, and human natural killer-1 synthesis. These findings demonstrate that LDN has significant impacts on N-glycan maturation in a completely different way from LacNAc, which could contribute to obtaining a comprehensive overview of the system regulating complex N-glycan biosynthesis.Lire moins >
Lire la suite >Structural variation of N-glycans is essential for the regulation of glycoprotein functions. GalNAcβ1-4GlcNAc (LacdiNAc or LDN), a unique subterminal glycan structure synthesized by B4GALNT3 or B4GALNT4, is involved in the clearance of N-glycoproteins from the blood and maintenance of cell stemness. Such regulation of glycoprotein functions by LDN is largely different from that by the dominant subterminal structure, N-acetyllactosamine (Galβ1-4GlcNAc, LacNAc). However, the mechanisms by which B4GALNT activity is regulated and how LDN plays different roles from LacNAc remain unclear. Here, we found that B4GALNT3 and four have unique domain organization containing a noncatalytic PA14 domain, which is a putative glycan-binding module. A mutant lacking this domain dramatically decreases the activity toward various substrates, such as N-glycan, O-GalNAc glycan, and glycoproteins, indicating that this domain is essential for enzyme activity and forms part of the catalytic region. In addition, to clarify the mechanism underlying the functional differences between LDN and LacNAc, we examined the effects of LDN on the maturation of N-glycans, focusing on the related glycosyltransferases upstream and downstream of B4GALNT. We revealed that, unlike LacNAc synthesis, prior formation of bisecting GlcNAc in N-glycan almost completely inhibits LDN synthesis by B4GALNT3. Moreover, the presence of LDN negatively impacted the actions of many glycosyltransferases for terminal modifications, including sialylation, fucosylation, and human natural killer-1 synthesis. These findings demonstrate that LDN has significant impacts on N-glycan maturation in a completely different way from LacNAc, which could contribute to obtaining a comprehensive overview of the system regulating complex N-glycan biosynthesis.Lire moins >
Langue :
Anglais
Audience :
Internationale
Vulgarisation :
Non
Établissement(s) :
Université de Lille
CNRS
CNRS
Équipe(s) de recherche :
Régulation de la glycosylation terminale
Date de dépôt :
2024-06-26T09:10:28Z
2024-06-28T06:48:45Z
2024-06-28T06:50:08Z
2024-06-28T06:48:45Z
2024-06-28T06:50:08Z
Fichiers
- P24.12 Tokora Kizuka 2024 JBC B4GALNT3 PA14 domain.pdf
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