Titre
Proteolysis of HCF-1 by Ser/Thr glycosylation-incompetent O-GlcNAc transferase:UDP-GlcNAc complexes.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Kapuria, V.
Auteure/Auteur
Röhrig, U.F.
Auteure/Auteur
Bhuiyan, T.
Auteure/Auteur
Borodkin, V.S.
Auteure/Auteur
van Aalten, D.M.
Auteure/Auteur
Zoete, V.
Auteure/Auteur
Herr, W.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1549-5477
Statut éditorial
Publié
Date de publication
2016
Volume
30
Numéro
8
Première page
960
Dernière page/numéro d’article
972
Peer-reviewed
Oui
Langue
anglais
Résumé
In complex with the cosubstrate UDP-N-acetylglucosamine (UDP-GlcNAc),O-linked-GlcNAc transferase (OGT) catalyzes Ser/ThrO-GlcNAcylation of many cellular proteins and proteolysis of the transcriptional coregulator HCF-1. Such a dual glycosyltransferase-protease activity, which occurs in the same active site, is unprecedented and integrates both reversible and irreversible forms of protein post-translational modification within one enzyme. Although occurring within the same active site, we show here that glycosylation and proteolysis occur through separable mechanisms. OGT consists of tetratricopeptide repeat (TPR) and catalytic domains, which, together with UDP-GlcNAc, are required for both glycosylation and proteolysis. Nevertheless, a specific TPR domain contact with the HCF-1 substrate is critical for proteolysis but not Ser/Thr glycosylation. In contrast, key catalytic domain residues and even a UDP-GlcNAc oxygen important for Ser/Thr glycosylation are irrelevant for proteolysis. Thus, from a dual glycosyltransferase-protease, essentially single-activity enzymes can be engineered both in vitro and in vivo. Curiously, whereas OGT-mediated HCF-1 proteolysis is limited to vertebrate species, invertebrate OGTs can cleave human HCF-1. We present a model for the evolution of HCF-1 proteolysis by OGT.
PID Serval
serval:BIB_244E53CD37D3
PMID
Open Access
Oui
Date de création
2016-04-25T07:03:32.149Z
Date de création dans IRIS
2025-05-20T20:11:37Z
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Nom
960 (2).pdf
Version du manuscrit
published
Taille
1021.78 KB
Format
Adobe PDF
PID Serval
serval:BIB_244E53CD37D3.P005
URN
urn:nbn:ch:serval-BIB_244E53CD37D30
Somme de contrôle
(MD5):d439bbd343f095c8dd25648936c24088