Binding of spectrin to hereditary spherocyte membranes

The structural instability of red cells from hereditary spherocytic patients suggests that the primary molecular alteration in this disorder resides in the spectrin membrane skeleton, a macromolecular structure thought to control red cell shape. In this study, the protein composition of HS red cell ghosts, spectrin-depleted inverted vesicles, and spectrin heterodimers was quantitatively normal in 9 HS patients from 3 unrelated families. The binding of ³²P-spectrin heterodimers to spectrin-depleted inverted vesicles (physiological ionic strength, pH 7.5, 4°C) indicated a K_D of 18.6 ± 2.0 nm (mean ± s.e.) and a maximal binding capacity of 98 ± 7 μg of spectrin bound/mg of inverted vesicle protein for 9 HS patients, and 18.3 ± 1.8 nm and 116 ± 8 μg spectrin/mg of inverted vesicle protein in 9 paired normal controls. Therefore the binding of spectrin to the syndeins (Bands 2.1 → 2.6) its high affinity membrane binding site, is unaltered in hereditary spherocytosis.