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Next Article 
Subunit assembly of hemoglobin: an important determinant of hematologic
phenotype
HF Bunn
Hemoglobin's physiologic properties depend on the orderly assembly of its
subunits in erythropoietic cells. The biosynthesis of alpha- and
beta-globin polypeptide chains is normally balanced. Heme rapidly binds to
the globin subunit, either during translation or shortly thereafter. The
formation of the alpha beta-dimer is facilitated by electrostatic
attraction of a positively charged alpha-subunit to a negatively charged
beta-subunit. The alpha beta-dimer dissociates extremely slowly. The
difference between the rate of dissociation of alpha beta- and alpha
gamma-dimers with increasing pH explains the well-known alkaline resistance
of Hb F. Two dimers combine to form the functioning alpha 2 beta
2-tetramer. This model of hemoglobin assembly explains the different levels
of positively charged and negatively charged mutant hemoglobins that are
encountered in heterozygotes and the effect of alpha-thalassemia and heme
deficiency states in modifying the level of the variant hemoglobin as well
as Hb A2. Electrostatic interactions also affect the binding of hemoglobin
to the cytoplasmic surface of the red cell membrane and may underlie the
formation of target cells. Enhanced binding of positively charged variants
such as S and C trigger a normally dormant pathway for potassium and water
loss. Thus, the positive charge on beta c is responsible for the two major
contributors to the pathogenesis of Hb SC disease: increased proportion of
Hb S and increased intracellular hemoglobin concentration. It is likely
that electrostatic interactions play an important role in the assembly of a
number of other multisubunit macromolecules, including membrane receptors,
cytoskeletal proteins, and DNA binding proteins.
Volume 69,
Issue 1,
pp. 1-6,
01/01/1987
Copyright © 1987 by The American Society of Hematology
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