Fig. (6).

Post-SET mediated auto-inhibition. A few SET domain PMT structures are characterized by a lack of peptide binding groove (top – the expected location of the groove is indicated by an arrow). In the structures of SETD2, SETMAR and NSD1 (yellow), a side-chain of the Post-SET domain is inserted into the substrate lysine channel, which results in a large shift of the Post-SET backbone that occupies the substrate- binding groove. We propose that this represents a mechanism of auto-inhibition. GLP in complex with an H3K9me peptide is shown here as a reference structure (Post-SET is blue, I-SET is cyan, substrate lysine is magenta, PDB code 3hna).