Fig. 1.

Spatial mutation clustering in KRAS. (A) Protein sequence of KRAS (Isoform 2B; UniProt: P01116-2) with mutated residues from the PanCancer data set (3) shown in red. Recurrent mutations (at least three samples) are shown in larger font and are annotated with position and number of samples with such mutations. Gray arcs between such residues are shown if their centroids are located closer than 13 Å between each other in the protein structure; arc width and label show the spatial distance in these cases (wider arcs corresponding to shorter distances). The C-terminal part of the protein sequence not covered by the structure in B is shown in smaller, gray font. (B) 3D structure of KRAS (gray) with substrate GDP (blue) bound to its active site (PDB ID code 4LUC) (7). Mutated residues are shown in red (recurrent mutations: sticks, nonrecurrent mutations: thin lines) and color intensity scales with the number of mutations per residue.