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Recognition of a glycosylation substrate by the O-GlcNAc transferase TPR repeats.

ABSTRACT: O-linked N-acetylglucosamine (O-GlcNAc) is an essential and dynamic post-translational modification found on hundreds of nucleocytoplasmic proteins in metazoa. Although a single enzyme, O-GlcNAc transferase (OGT), generates the entire cytosolic O-GlcNAc proteome, it is not understood how it recognizes its protein substrates, targeting only a fraction of serines/threonines in the metazoan proteome for glycosylation. We describe a trapped complex of human OGT with the C-terminal domain of TAB1, a key innate immunity-signalling O-GlcNAc protein, revealing extensive interactions with the tetratricopeptide repeats of OGT. Confirmed by mutagenesis, this interaction suggests that glycosylation substrate specificity is achieved by recognition of a degenerate sequon in the active site combined with an extended conformation C-terminal of the O-GlcNAc target site.

SUBMITTER: Rafie K

PROVIDER: S-EPMC5493779 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Recognition of a glycosylation substrate by the O-GlcNAc transferase TPR repeats.

Rafie Karim K Raimi Olawale O Ferenbach Andrew T AT Borodkin Vladimir S VS Kapuria Vaibhav V van Aalten Daan M F DMF

Open biology 20170601 6

O-linked <i>N</i>-acetylglucosamine (O-GlcNAc) is an essential and dynamic post-translational modification found on hundreds of nucleocytoplasmic proteins in metazoa. Although a single enzyme, O-GlcNAc transferase (OGT), generates the entire cytosolic O-GlcNAc proteome, it is not understood how it recognizes its protein substrates, targeting only a fraction of serines/threonines in the metazoan proteome for glycosylation. We describe a trapped complex of human OGT with the C-terminal domain of T ...[more]

PMID: 28659383

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