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Biophysical characterization of the alpha-globin binding protein alpha-hemoglobin stabilizing protein

Citation

Gell, D and Kong, Y and Eaton, SA and Weiss, MJ and Mackay, JP, Biophysical characterization of the alpha-globin binding protein alpha-hemoglobin stabilizing protein, Journal of Biological Chemistry, 277, (43) pp. 40602-40609. ISSN 0021-9258 (2002) [Refereed Article]

DOI: doi:10.1074/jbc.M206084200

Abstract

α-Hemoglobin stabilizing protein (AHSP) is a small (12 kDa) and abundant erythroid-specific protein that binds specifically to free α-(hemo)globin and prevents its precipitation. When present in excess over β-globin, its normal binding partner, α-globin can have severe cytotoxic effects that contribute to important human diseases such as β-thalassemia. Because AHSP might act as a chaperone to prevent the harmful aggregation of α-globin during normal erythroid cell development and in diseases of globin chain imbalance, it is important to characterize the biochemical properties of the AHSP·α-globin complex. Here we provide the first structural information about AHSP and its interaction with α-globin. We find that AHSP is a predominantly α-helical globular protein with a somewhat asymmetric shape. AHSP and α-globin are both monomeric in solution as determined by analytical ultracentrifugation and bind each other to form a complex with 1:1 subunit stoichiometry, as judged by gel filtration and amino acid analysis. We have used isothermal titration calorimetry to show that the interaction is of moderate affinity with an association constant of 1 × 107 M-1 and is thus likely to be biologically significant given the concentration of AHSP (∼0.1 mM) and hemoglobin (∼4 mm) in the late pro-erythroblast.

Item Details

Item Type:Refereed Article
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
Author:Gell, D (Dr David Gell)
ID Code:64569
Year Published:2002
Web of Science® Times Cited:77
Deposited By:Menzies Institute for Medical Research
Deposited On:2010-08-12
Last Modified:2011-08-02
Downloads:0

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