Figure 3: Stabilization of the SET-I region.
From: Structural basis of oncogenic histone H3K27M inhibition of human polycomb repressive complex 2
The active conformation of the SET domain is stabilized by interactions with the Vefs domain and with the SAL and SRM from the N terminus of EZH2. (a) Superposition of the human EZH2 SET domain from the PRC2 complex structure (blue) with isolated domain (PDB 4MI5, red). There are three main regions stabilized by interactions in the complex (b). The conserved GxG loop is stabilized by interactions with the SAL subdomain from the N terminus of EZH2 (orange) and the region N-terminal to the SUZ12 Vefs domain (grey). (c) The SAL subdomain region of EZH2 (orange) also makes a series of main chain interactions with the SET-I region, contributing to the stabilization of the domain and the ordering of the active site. (d) There is a significant change in the conformation of the C terminus of the SET domain in the complex to support the completion of the active site.
