Structurally similar large ankyrin loops alternate with small ankyrin loops in IκBα. IκBα Ank3 (green) is shown superimposed on IκBα Ank5 (light green) to illustrate corresponding structural features. Alternating small and large ankyrin loops seem to be a conserved feature of vertebrate and invertebrate NF-κB binding ankyrins, suggesting a "lock and key" mechanism. ZEBRA is proposed to mimic both large ankyrin loop structures and small ankyrin loop structures in order to fit into the NF-κB binding code. The bulge region of Ank3 and Ank5, although encoded by different primary amino acids both can form a structure corresponding to the helix structure found in ZANK (Figure 9). IκBα Ank3, Ank5, and potentially ZANK, also share conserved orientation of aromatic and bulky amino acids in the loop regions not present in IκBα Ank4.