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Proteolytic Cleavage Driven by Glycosylation

TitleProteolytic Cleavage Driven by Glycosylation
Publication TypeJournal Article
Year of Publication2016
AuthorsKoetzler, MP, Withers, SG
JournalJOURNAL OF BIOLOGICAL CHEMISTRY
Volume291
Pagination429-434
Date PublishedJAN 1
ISSN0021-9258
Abstract

Proteolytic processing of human host cell factor 1 (HCF-1) to its mature form was recently shown, unexpectedly, to occur in a UDP-GlcNAc-dependent fashion within the transferase active site of O-GlcNAc-transferase (OGT) (Lazarus, M. B., Jiang, J., Kapuria, V., Bhuiyan, T., Janetzko, J., Zandberg, W. F., Vocadlo, D. J., Herr, W., and Walker, S. (2013) Science 342, 1235-1239). An interesting mechanism involving formation and then intramolecular rearrangement of a covalent glycosyl ester adduct of the HCF-1 polypeptide was proposed to account for this unprecedented proteolytic activity. However, the key intermediate remained hypothetical. Here, using a model enzyme system for which the formation of a glycosyl ester within the enzyme active site has been shown unequivocally, we show that ester formation can indeed lead to proteolysis of the adjacent peptide bond, thereby providing substantive support for the mechanism of HCF-1 processing proposed.

DOI10.1074/jbc.C115.698696