Studies on the structural polymorphism of the alpha-II domain of human erythrocyte spectrin.

Following restricted tryptic digestion at 4 degrees C, a structural polymorphism affecting the alpha-chain of human spectrin, the major erythrocyte membrane skeleton protein, has recently been described in American blacks (Knowles, W.J., Bologna, M.L., Chasis, J.A., Marchesi, S.L. and Marchesi, V.T. (1984) J. Clin. Invest 73, 973-979). Four variants affecting the alpha-II domain or its tryptic products have been characterized, depending on changes in molecular weight and/or isoelectric point. One variant of the alpha-II domain (Type 2) shows an increase in apparent molecular weight and basic shift in pI. It contains a limit chymotryptic peptide showing a change in chromatographic mobility on two-dimensional electrophoresis which is thought to reflect a sequence alteration associated with the increase in apparent molecular weight. We find that this altered limit chymotryptic peptide is not unique to the Type 2 variant, but is also present in a variant (Type 4) showing only the same basic shift in pI as the Type 2 variant. It is not found in a variant (Type 3) showing only an increase in apparent molecular weight. The most likely explanation for these findings is that the altered limit chymotryptic peptide common to both the Type 2 and Type 4 variants is responsible for the change in isoelectric point which is common to both these variants. An as yet unidentified change elsewhere in the polypeptide chain must be responsible for the observed alteration in molecular weight of the Types 2 and 3 variants.