Schematic of human erythrocyte spectrin. (A) Both the α (top) and β (bottom) isoforms of erythroid spectrin are composed of many tandem 3-helix bundle motifs (each helix is depicted as a cylinder). In the case of α-spectrin, 20 full repeats and 1 partial repeat at the N-terminus (light blue) make up the majority of the molecule. For historical reasons, the SH3 domain, located between the B and C helix of repeat α9, is assigned as the α10 motif. Similarly, β-spectrin possesses 16 full repeats and 1 partial repeat at the C-terminus (yellow). Selected regions of each spectrin isoform with a particular structure or function are colored. (B) Spectrin assembly in red cells begins with dimerization of α and β chains that is nucleated by specialized dimerization repeats (red). Subsequent tetramer formation occurs through head-to-head interaction of the tetramerization domains. (C) An enlarged schematic of the molecular components presented in this study that includes α-spectrin repeats 0-1 and β-spectrin repeats 16-17.