Extended Data Figure 9: Crystal structures of the BRS domain and the BRS:CC-SAM complex.
From: MEK drives BRAF activation through allosteric control of KSR proteins
a, X-ray data collection and refinement statistics table for the crystal structures of the hBRS domain and the hCC–SAM–hBRS complex. b, Ribbon representation of the crystal structure of the BRS domain of human BRAF. Residues comprising the hydrophobic core of the coiled-coil interactions are shown as sticks. c, Structure of the BRAF BRS and KSR1 CC-SAM domain complex. Contents of the asymmetric unit revealed two CC-SAM:BRS complexes interacting in trans. Disordered (GS)4 linker between CC-SAM and BRS domains is represented by dashed lines. The connectivity between the BRS and the CC-SAM domains was deduced as trans because in this configuration, but not the cis configuration, the C terminus of the CC-SAM domain is sufficiently close to the N terminus of the BRS domain (15 Å) to be physically spanned by the disordered linker comprising 15 amino-acid residues. For comparison, the connection in cis would need to minimally span 80 Å. d, Representative final 2Fo − Fc electron density map contoured at 1.0σ for the BRS:CC-SAM complex at a region of drastic conformational rearrangement in CC-SAM relative to the isolated CC-SAM structure (indicated by the arrow). e, SEC–MALS analysis of the indicated crystallization fusion proteins (top). The horizontal black, red, and green lines correspond to SEC–MALS calculated masses for the indicated fusion proteins. Summary table (bottom) of measured and theoretical calculated molecular masses for each protein complex analysed. Experiments were performed in triplicate.
