Electrostatic interactions in the assembly of haemoglobin.

Haemoglobin is the prototype of an allosteric protein in which cooperative behaviour depends on interaction between unlike subunits. Here we present haematological and biochemical evidence that electrostatic interactions are an important determinant of haemoglobin assembly. Individuals heterozygous for positively charged beta-globin variants have a significantly lower proportion of abnormal haemoglobin than those with negatively charged variants. Moreover, these differences become more pronounced when alpha-thalassaemia is also present. Kinetic experiments using isolated chains indicate that the rate of assembly of the heterotetramer is influenced by alterations in surface charge. A simple electrostatic model is proposed in an attempt to explain these haematological and experimental findings.