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Alpha-hemoglobin stabilizing protein: molecular function and clinical correlation
Chairat Turbpaiboon1,Prapon Wilairat1
1
Department of Biochemistry, Faculty of Science, Mahidol University, Rama 6 Road, Bangkok 10400, Thailand
DOI: 10.2741/3601 Volume 15 Issue 1, pp.1-11
Published: 01 January 2010
(This article belongs to the Special Issue Molecular chaperone genes in the human genome)
Abstract

The discovery of alpha-hemoglobin stabilizing protein (AHSP), a chaperone for free alpha-hemoglobin (alpha-Hb), has provided a satisfactory solution to the perplexing problem of balanced globin levels for Hb production in erythroid cells in the face of a two-fold excess of alpha-globin to beta-globin gene dosage. Unmatched alpha-Hb is unstable and precipitates onto membranes, where the released heme exerts oxidative damages resulting in ineffective erythropoiesis and hemolytic anemia, the underlying causes of pathology in the hereditary anemia of beta-thalassemia. The interaction of alpha-Hb with AHSP involves surfaces normally employed in binding to beta-Hb. However, a conformational change to the AHSP-bound alpha-Hb results in an oxidized heme, but in a pocket that is now less exposed to the outside environment, thereby protecting against both peroxide-induced heme loss and iron-induced redox reaction. Studies in both mice and humans indicate that reduction in AHSP can result in hematological pathology. Conversely, alpha-Hb variants that are compromised in their ability to bind with AHSP produce beta-thalassemia-like symptoms. Disease conditions like some forms of thalassemia that are directly associated with AHSP structural and/or functional defects can now be included within the category of chaperonopathies.

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Chairat Turbpaiboon, Prapon Wilairat. Alpha-hemoglobin stabilizing protein: molecular function and clinical correlation. Frontiers in Bioscience-Landmark. 2010. 15(1); 1-11.