Alignment of IκBα Ank3 and Ank4 Helices. IκBα Ank3 (green) and Ank4 (yellow) domains are extracted from the NF-κB p65/p50 dimer bound structure and are shown superimposed to illustrate the highly conserved structure of the stem and the less conserved loop region. Ank3 loop has a bulge not present in Ank4. Ank3 also has more bulky hydrophobic residues than Ank4 in the region of the loop extending most deeply into the NF-κB p65/p50 structure. Arrows illustrate key features of Ank3 and Ank4 including a highly conserved His residue shared by most ankyrin stems (Ank3, His 149; Ank4, His 188). Also shown are bulky residues in Ank3 (Tyr 181 and His184) present in Ank4.