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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 recognises 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 transferase
- Substrate recognition
Rafie, K., Raimi, O., Ferenbach, A. T., Borodkin, V. S., Kapuria, V., & van Aalten, D. M. F. (2017). Recognition of a glycosylation substrate by the O-GlcNAc transferase TPR repeats. Open Biology, 7, 1-9. . https://doi.org/10.1098/rsob.170078