Fig. 9: Summary of the results of this study.

a Preferred hairpin formation of ssK36 in solution due to favourable intrapeptide contacts. b Accelerated binding of the hairpin into the SETD2 peptide binding cleft with the K36 facing outside. c Unfolding of the hairpin conformation in the SETD2-peptide complex by specific enzyme-peptide contacts in a zipper-like process leading to the adoption of an extended peptide conformation. d Distinct contact networks lead to different TS-like conformations and better stabilization of TS-like conformation of ssK36 than H3K36.