Open Biol.: co-auth.: V.Kapuria (group Herr)

Open Biol. 2017 Jun;7(6). pii: 170078. doi: 10.1098/rsob.170078.

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


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.


O-GlcNAc; O-GlcNAc transferase; glycosylation; signalling; substrate recognition

PMID: 28659383