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Adult haemoglobin (Hb) is made up of two α and two β subunits. Mutations that reduce expression of the α- or β-globin genes lead to the conditions α- or β-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 β chains that is conferred through β self-association. In contrast, α subunits interact weakly, and in the absence of stabilizing quaternary interactions the α chain (α) is prone to haem loss and denaturation. The molecular contacts that confer weak self-association of α have not been determined previously. Here, the first structure of an α2 homodimer is reported in complex with one domain of the Hb receptor from Staphylococcus aureus. The α2 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 α1β1 dimer interface of native Hb are preserved in the α2 dimer. However, a marked asymmetry is observed in the α2 interface, suggesting that steric factors limit the number of stabilizing interactions that can form simultaneously across the interface.

Item Type:	Refereed Article
Keywords:	Hb Bart's; HbH; IsdHN1; Staphylococcus aureus; homodimer; α-haemoglobin
Research Division:	Biological Sciences
Research Group:	Biochemistry and Cell Biology
Research Field:	Structural Biology (incl. Macromolecular Modelling)
Objective Division:	Expanding Knowledge
Objective Group:	Expanding Knowledge
Objective Field:	Expanding Knowledge in the Biological Sciences
UTAS Author:	Gell, DA (Dr David Gell)
ID Code:	93509
Year Published:	2014
Web of Science® Times Cited:	2
Deposited By:	Menzies Institute for Medical Research
Deposited On:	2014-08-06
Last Modified:	2017-11-06
Downloads:	232 View Download Statistics