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

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

Blog Article

O-linked N-acetylglucosamine (O-GlcNAc) is an essential and dynamic post-translational modification found on hundreds of nucleocytoplasmic chicago cubs earrings 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 att nighthawk hotspot conformation C-terminal of the O-GlcNAc target site.