Competition of normal β chains and sickle haemoglobin β chains for α chains as a post-translational control mechanism

Abstract

ADULT human haemoglobin (HbA) is a tetrameric protein with two α and two β polypeptide chains. Theoretically, individuals heterozygous for a β-chain mutation should have equal amounts of the normal HbA (α^A₂β^A₂) and an abnormal variant (α^A₂β^X₂) in their red cells. However, these people usually have different amounts of the two haemoglobins. For example, the red cells of sickle cell trait individuals usually contain about 60% HbA and 40% HbS^1–5. Those who also have an α-thalassaemia gene(s), which decreases production of α chains, have an even lower proportion of HbS^6–12. Each of these two haemoglobin polymers has an α-chain type common to both proteins as well as a specific β^A or β^S chain type. The individual α, β^A, and β^S chain types can be isolated in vitro in a functional form so that the haemoglobin tetramers can be reconstituted from appropriate mixtures of α and β chains¹³. Here we report that more HbA than HbS was formed when a mixture of equal amounts of β^A and β^S chains was incubated with limiting concentrations of α chains. These results suggest that a similar form of post-translational control of haemoglobin assembly may exist in some erythroid cells in vivo. The accomplishment of these experiments and the interpretation of the results were greatly facilitated by the use of radiolabelled haemoglobin chains of high specific activity.