Proteolysis of HCF-1 by Ser/Thr glycosylation-incompetent O-GlcNAc transferase:UDP-GlcNAc complexes.

Détails

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Etat: Serval
Version: Final published version
ID Serval
serval:BIB_244E53CD37D3
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Proteolysis of HCF-1 by Ser/Thr glycosylation-incompetent O-GlcNAc transferase:UDP-GlcNAc complexes.
Périodique
Genes and Development
Auteur(s)
Kapuria V., Röhrig U.F., Bhuiyan T., Borodkin V.S., van Aalten D.M., Zoete V., Herr W.
ISSN
1549-5477 (Electronic)
ISSN-L
0890-9369
Statut éditorial
Publié
Date de publication
2016
Peer-reviewed
Oui
Volume
30
Numéro
8
Pages
960-972
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.
Mots-clé
Amino Acid Motifs, Animals, Catalytic Domain, Computer Simulation, Evolution, Molecular, Host Cell Factor C1/metabolism, Humans, Invertebrates/enzymology, Models, Molecular, Mutation, N-Acetylglucosaminyltransferases/metabolism, Protein Processing, Post-Translational, Protein Structure, Tertiary, Proteolysis
Pubmed
Web of science
Open Access
Oui
Création de la notice
25/04/2016 9:03
Dernière modification de la notice
08/05/2019 15:51
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