Schematic diagrams of erythrocyte β-spectrin and ankyrin. The schematic diagrams show the domain organization of the 2 molecules. (A) The intact human erythroid β-spectrin (HEβ) molecule consists mainly of tandem repeats of 3-helix bundles, each bundle known as a spectrin repeats (numbered from N to C terminus). The ankyrin binding domain comprises repeats 14 and 15 (light blue).^24,25,28  Additional binding domains include 2 N-terminal calponin homology (CH) domains responsible for actin binding (orange), spectrin repeats 1 and 2, which mediate α/β dimer formation (red), and a tetramerization domain consisting of a 2-helix bundle (ie, an incomplete repeat) near the C-terminus (green). (B) Human erythroid ankyrin (Ankyrin R) consists of an N-terminal membrane protein binding domain composed of ankyrin repeats (yellow), a central spectrin binding domain that harbors a ZU5-containing subdomain identified as the minimal binding domain for β-spectrin (ZU5-ANK) (red/pink), and a C-terminal regulatory domain that modulates the affinities of the other domains and contains a Death Domain (blue).