Fig. 2: Structural features of the p53 core domain when bound to Pol II.

a An overlay of cryo-EM density and p53/Pol II molecular structure is shown (left panel). A zoomed view highlights the p53 core domain and Pol II interface (right panel). The p53 core domain/Pol II cavity (red circle) is formed upon their interaction. The key DNA binding helix and helix 1 of the p53 core domain are indicated. b The molecular structure of the p53 core domain and Pol II around the interface is presented. The cavity is positioned in between Pol II’s Rpb1 clamp and DNA binding helices of the p53 core domain. Three hot-spot oncogenic residues (i.e., R175, R248 and R282, frequently mutated in cancer patients)^9,29, critical for sequence-specific DNA binding, are located around the surface of the core domain/Pol II cavity. c The structure of the closed PIC (PDB: RCSB 5IYA⁶, left panel) shows the positioning of Pol II and upstream DNA/GTFs, in comparison with the contact surfaces of p53-bound Pol II (right panel). The p53 core domain occupies the regions of Pol II in the vicinity of upstream DNA, TBP, TFIIA and TFIIB (compare both panels).