Extended Data Fig. 4: A putative RAS-binding region in HK1.

a, Crystal structure (PDB 4G0N) of the CRAF RBD (cyan and magenta) in complex with the G domain of HRAS (orange; nucleotide (grey) and magnesium (black)). The regions of the CRAF RBD that mediate the interaction with HRAS are magenta. b, Superposition of the N-terminal lobe of HK1 (green and magenta; PDB 4F9O) alongside HRAS (orange). The putative region of HK1 that interacts with RAS, corresponding to that of the CRAF RBD, is coloured magenta. c, A section of the helix–loop–sheet structure that is common to RBDs is superimposed on the region of HK1 highlighted in b. The RBD of CRAF is shown in cyan, BRAF (PDB 3NY5) in yellow and the putative RBD of HK1 in green. d, Sequence alignments of validated RBDs and the HK1 putative RBD shown with structural motifs of BRAF (yellow) and HK1 (green). Despite the highly conserved structural features shown in c, RBDs have little sequence homology.