Biochemical fates of α hemoglobin bound to α hemoglobin-stabilizing protein AHSP

Suiping Zhou, John S. Olson, Marian Fabian, Mitchell J. Weiss, Andrew J. Gow

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Alpha hemoglobin-stabilizing protein (AHSP) is an erythroid protein that binds free α hemoglobin (αHb) to maintain its structure and limit its pro-oxidant activity. Prior studies have defined two different αHb·AHSP complexes. Binding of AHSP to Fe(II) αHb induces an unusual configuration in which the F helix of the globin becomes disordered and the heme ring becomes solvent-exposed. Over time, this intermediate oxidizes to form a stable hemichrome in which the proximal (F8) and distal (E7) histidines are coordinated to the heme iron atom. The addition of βHb to either Fe(II) or Fe(III) αHb·AHSP displaces AHSP to generate tetrameric (α2β2) HbA species. The biochemical properties and in vivo significance of the two αHb·AHSP complexes are poorly understood. Here we show that Fe(III) αHb·AHSP forms from auto-oxidation of oxygenated αHb bound to AHSP and that this process is greatly accelerated at physiologic temperature and oxygen pressures. In contrast to free Fe(III) αHb hemichromes, AHSP-bound Fe(III) αHb does not precipitate and can be recycled into functional HbA. This requires enzymatic reduction of AHSP-bound αHb, either prior to or after extraction by β subunits. In contrast, reaction of Fe(II) αHb-AHSP with αHb generates functional HbA directly. Our findings support a model in which AHSP can either stabilize αHb transiently en route to HbA formation during normal erythropoiesis or convert excessive free αHb into a more chemically inert state from which recovery of αHb is possible by redox cycling.

Original languageEnglish
Pages (from-to)32611-32618
Number of pages8
JournalJournal of Biological Chemistry
Volume281
Issue number43
DOIs
Publication statusPublished - 27 Oct 2006
Externally publishedYes

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Hemoglobins
Proteins
Heme
Globins
Erythropoiesis
Histidine
Oxidation-Reduction
Precipitates
Reactive Oxygen Species

ASJC Scopus subject areas

  • Biochemistry

Cite this

Biochemical fates of α hemoglobin bound to α hemoglobin-stabilizing protein AHSP. / Zhou, Suiping; Olson, John S.; Fabian, Marian; Weiss, Mitchell J.; Gow, Andrew J.

In: Journal of Biological Chemistry, Vol. 281, No. 43, 27.10.2006, p. 32611-32618.

Research output: Contribution to journalArticle

Zhou, Suiping ; Olson, John S. ; Fabian, Marian ; Weiss, Mitchell J. ; Gow, Andrew J. / Biochemical fates of α hemoglobin bound to α hemoglobin-stabilizing protein AHSP. In: Journal of Biological Chemistry. 2006 ; Vol. 281, No. 43. pp. 32611-32618.
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