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

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State: Public
Version: Final published version
Serval ID
serval:BIB_244E53CD37D3
Type
Article: article from journal or magazin.
Collection
Publications
Title
Proteolysis of HCF-1 by Ser/Thr glycosylation-incompetent O-GlcNAc transferase:UDP-GlcNAc complexes.
Journal
Genes and Development
Author(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
Publication state
Published
Issued date
2016
Peer-reviewed
Oui
Volume
30
Number
8
Pages
960-972
Language
english
Abstract
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.
Keywords
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
Yes
Create date
25/04/2016 9:03
Last modification date
20/08/2019 14:02
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