SOME EFFECTS OF POSTTRANSLATIONAL N-TERMINAL ACETYLATION OF THE HUMANEMBRYONIC ZETA-GLOBIN PROTEIN

Using site-directed mutagenesis we have produced the first mutant form of a human embryonic haemoglobin. We have mutated the N-terminal Ser residue of the zeta-chain of haemoglobin Portland, zeta(2) gamma(2), ( which is normally acetylated) to a Val (which possesses a free amine t erminus). The protein spontaneously assembles into a fully functional tetramer which shows cooperative oxygen binding. Determination of the reactivity of the mutant protein with 2,3-diphosphoglycerate indicates that the mutation process does not lead to any major disruption of th e protein structure. A comparison of the properties of the mutant and wild-type proteins identifies a significant role for the normal N-term inal acetylation of the zeta-chain with regard to the alkaline Bohr ef fect and the sensitivity of the oxygen affinity of the protein towards chloride ions. The possible physiological significance of this modifi cation is discussed.