Residues adjacent to ζ-φ-x-x-φ-φ motif dictate mode of KIX recognition. (A) Sequence alignment of ζ-φ-x-x-φ-φ containing KIX-binding proteins. ζ indicates an acidic amino acid; φ, a bulky hydrophobic amino acid; and x, any amino acid. Conserved hydrophobic amino acid residues are colored yellow, acid residues red, and basic residues blue. Positions within the respective protein sequences are indicated as numbers. (B-G) Comparison of the orientation of PCET (orange ribbon) and MLL (red ribbon) on the KIX domain (gray ribbon/transparent surface for KIX bound to MLL and teal for KIX bound to HEB-PCET). Noteworthy residues from each activation domain are represented as sticks. (E-G) Views of panels B-D, respectively, that have been rotated clockwise 70 degrees about their x-axes. The KIX/MLL complex is from PDB accession 2AGH.