Spectrin structures and interactions and the anemia-causing linker mutant. (A) Antiparallel heterodimers of αI-spectrin (light) and β-spectrin (dark) associate head to tail to form a tetramer that crosslinks F-actin at the red blood cell membrane. Linkers between repeats were originally thought to be random coils, but recent evidence suggests many are helical. Normal and mutant constructs of the αI-spectrin N-terminus allow study of the effects of the pathogenic mutation Q471P, which is located in the linker between repeats α4 and 5. The table lists the melting temperature of the individually expressed repeats²  and the number of cysteines within each repeat. (B) Dimer-tetramer ratio for spectrin purified from control and patient blood, with model fits that yield a weaker dissociation constant K_d-tetramer for the Q471P mutant (data not shown). (inset) A 2% to 4% gradient nondenaturing polyacrylamide gel of spectrin from control and patient erythrocytes. Lanes 1 to 5 contain WT sample spectrin concentrations of 11, 6, 3, 1, and 0.5 mg/dL. Lanes 6 to 11 contain hereditary elliptocytosis patient spectrin concentrations of 15, 11, 6, 3, 1, and 0.5 mg/dL.