Influence of gamma-chain amino-terminal acetylation on subunit assembly of human fetal hemoglobin.
A human hemoglobin F subunit recombination study was performed to determine the relative efficiency of recombination of amino-terminally acetylated gamma-chains and non-acetylated chains with alpha-chains. The results of this work suggested that the acetylated gamma Ic-chains combined more readily with the alpha-chains than the non-acetylated gamma o-chains. An important factor in the function and assembly of multi-subunit macromolecules is the interaction of the unlike subunits. A model system for the study of such interactions has been the protein hemoglobin. With respect to the hemoglobin molecule, it has been noted that relative affinities of normal and mutant subunits for the unlike subunits can have a significant influence on hemoglobin synthesis at the post-translation level, i.e., subunit assembly [1,2]. A similar mechanism may control the formation of human Hb FIc, a hemoglobin with NH2-terminally acetylated gamma- (gamma Ic)-chains. In this instance acetylation may occur on the ribosomes before subunit assembly. A previous report from our laboratory showed a slight increase in the relative proportion of Hb FIc in cord blood samples with over 5% Hb Bart's [3]. The data were interpreted to be due to an influence of alpha-chain deficiency (alpha-thalassemia) on the formation of Hb FIc and Hb Fo tetramers by a preference of alpha-chains for gamma Ic-chains over gamma o- (non-acetylated gamma)-chains. The present study involves an examination of the relative affinity of the gamma Ic- and gamma o-chains for the normal alpha-chains in an in vitro recombination system.
D000107:Acetylation; D000595:Amino Acid Sequence; D005319:Fetal Hemoglobin / Q000031:analogs & derivatives* / Q000378:metabolism; D006455:Hemoglobins, Abnormal / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational
D006455:Hemoglobins, Abnormal; C028560:acetylated human fetal hemoglobin; D005319:Fetal Hemoglobin; C030448:hemoglobin Bart's