Figure 4: Activation of PRC2 by the Jarid2 K116me3 peptide.
From: Structural basis of oncogenic histone H3K27M inhibition of human polycomb repressive complex 2
(a–d) In this figure, a,c and d are shown in the same orientation as Fig. 1a, while b is an alternative view selected to highlight the interactions of Arg(−1). For clarity, a number of Jarid2 side chains have been omitted. (a) Surface representation of EED and unbiased Fourier Map (Fo-Fc contoured at 2σ) showing the binding of the repressive trimethyl peptide from Jarid2 (yellow). The methylated lysine (K116me3) binds in a defined pocket on the surface of EED. (b) Stick representation of repressive peptide (yellow) making interactions with EED (white) and with the SRM subdomain of EZH2N. The interaction between the conserved Arg(−1) side chain and the SRM is important for positioning of the SRM, which in turn stabilizes the SET-I helix to activate catalysis. (c) The interactions between repressive peptide, EED and the SRM. (d) Although the Jarid peptide (human structure) and the H3K27me3 peptide (yeast structure) occupy the same binding site in EED, in the yeast structure the crucial Arg(−1) side chain does not bind to the SRM. (e) Surface representation of EED, the SRM subdomain (pink) and SET domain (blue) are shown in cartoon representation with key residues as sticks. The Jarid2 peptide (yellow) binds to EED, this stabilizes the SRM, which in turn stabilizes the SET-I facilitating methylation of the H3K27 target (green). (f) A schematic showing the hydrophobic interactions between the SRM (helix residues in black, extended chain residues in red) and the SET-I.
