National Center for
3S48: Human Alpha-haemoglobin Complexed With The First Neat Domain Of Isdh From Staphylococcus Aureus
The structure of alpha-haemoglobin in complex with a haemoglobin-binding domain from Staphylococcus aureus reveals the elusive alpha-haemoglobin dimerization interface
Acta Crystallogr F Struct Biol Commun (2014) 70 p.1032-1037
Adult haemoglobin (Hb) is made up of two alpha and two beta subunits. Mutations that reduce expression of the alpha- or beta-globin genes lead to the conditions alpha- or beta-thalassaemia, respectively. Whilst both conditions are characterized by anaemia of variable severity, other details of their pathophysiology are different, in part owing to the greater stability of the beta chains that is conferred through beta self-association. In contrast, alpha subunits interact weakly, and in the absence of stabilizing quaternary interactions the alpha chain (alpha) is prone to haem loss and denaturation. The molecular contacts that confer weak self-association of alpha have not been determined previously. Here, the first structure of an alpha2 homodimer is reported in complex with one domain of the Hb receptor from Staphylococcus aureus. The alpha2 dimer interface has a highly unusual, approximately linear, arrangement of four His side chains within hydrogen-bonding distance of each other. Some interactions present in the alpha1beta1 dimer interface of native Hb are preserved in the alpha2 dimer. However, a marked asymmetry is observed in the alpha2 interface, suggesting that steric factors limit the number of stabilizing interactions that can form simultaneously across the interface.