Fig. 1: Cryo-EM structure of inhibitor-bound BRAF2:14-3-32 dimer complex.
From: Structural insights into the BRAF monomer-to-dimer transition mediated by RAS binding
a BRAF domain organization is shown with color coding: RAS binding domain (RBD, red orange), cysteine-rich domain (CRD, purple), and the kinase domain (KD, blue). BRAF residues S365 (green) and S729 (dark red) serve as 14-3-3-binding sites when phosphorylated. b Cryo-EM density map at 3.9 Å resolution (left) and structure (right) of the BRAF2:14-3-32 complex. BRAF domains are colored as in a, with one KD protomer in light blue and the other in dark blue. SB590885 is shown in coral and the 14-3-3 dimer is colored gold. c Superposition of the SB590885-liganded BRAF2:14-3-32 structure (colored as in b) with the previously reported cryo-EM structure of the unliganded BRAF2:14-3-32 complex in gray (PDB ID: 6UAN) is shown with a Cα RMSD of 1.54 Å for the overall structure. The inset demonstrates that residues F743-A749 in the C-tail end (in red) of the unliganded complex (PDB ID: 6UAN) and the BRAF inhibitor SB590885 (in coral) of the present structure occupy overlapping positions in the active site.
