CARBOXYL-TERMINAL MODIFICATION INFLUENCES SUBUNIT ASSEMBLY OF SICKLE HEMOGLOBIN BETA-CHAINS

The subunit assembly properties of isolated beta and Des(His-146, Tyr- 145)beta chains of sickle hemoglobin were investigated by isoelectric focusing over a protein concentration range from 500-125 mu M in heme. Two components (presumably tetramer and monomer) and three components (designated tetramer, dimer and monomer) were visualized for beta(S) and Des(His-146,Tyr-145)beta(S) chains, respectively. Intensitometric quantitation of Des(His-146,Tyr-145)beta(S) chains demonstrated a simi lar distribution of all three structural components before and after t he addition of their heteropartner alpha chains. This is in direct con trast to the reported preferential loss of Des(His-146,Tyr-145)beta(A) monomer species upon assembly and points to a major role of the beta( 6) residue in the overall structural homeostasis of carboxylterminal m odified human beta chains. (C) 1996 Academic Press, Inc.