Structure of oxidized α-haemoglobin bound to AHSP reveals a protective mechanism for haem

Liang Feng, Suiping Zhou, Lichuan Gu, David A. Gell, Joel P. Mackay, Mitchell J. Weiss, Andrew J. Gow, Yigong Shi

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

The synthesis of haemoglobin A (HbA) is exquisitely coordinated during erythrocyte development to prevent damaging effects from individual α- and β-subunits. The α-haemoglobin-stabilizing protein (AHSP) binds α-haemoglobin (αHb), inhibits the ability of αHb to generate reactive oxygen species and prevents its precipitation on exposure to oxidant stress. The structure of AHSP bound to ferrous αHb is thought to represent a transitional complex through which αHb is converted to a non-reactive, hexacoordinate ferric form. Here we report the crystal structure of this ferric αHb-AHSP complex at 2.4 A resolution. Our findings reveal a striking bis-histidyl configuration in which both the proximal and the distal histidines coordinate the haem iron atom. To attain this unusual conformation, segments of αHb undergo drastic structural rearrangements, including the repositioning of several α-helices. Moreover, conversion to the ferric bishistidine configuration strongly and specifically inhibits redox chemistry catalysis and haem loss from αHb. The observed structural changes, which impair the chemical reactivity of haem iron, explain how AHSP stabilizes αHb and prevents its damaging effects in cells.

Original languageEnglish
Pages (from-to)697-701
Number of pages5
JournalNature
Volume435
Issue number7042
DOIs
Publication statusPublished - 2 Jun 2005
Externally publishedYes

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Heme
Hemoglobins
Iron
Hemoglobin A
Catalysis
Histidine
Oxidants
Oxidation-Reduction
Reactive Oxygen Species
Erythrocytes

ASJC Scopus subject areas

  • General

Cite this

Feng, L., Zhou, S., Gu, L., Gell, D. A., Mackay, J. P., Weiss, M. J., ... Shi, Y. (2005). Structure of oxidized α-haemoglobin bound to AHSP reveals a protective mechanism for haem. Nature, 435(7042), 697-701. https://doi.org/10.1038/nature03609

Structure of oxidized α-haemoglobin bound to AHSP reveals a protective mechanism for haem. / Feng, Liang; Zhou, Suiping; Gu, Lichuan; Gell, David A.; Mackay, Joel P.; Weiss, Mitchell J.; Gow, Andrew J.; Shi, Yigong.

In: Nature, Vol. 435, No. 7042, 02.06.2005, p. 697-701.

Research output: Contribution to journalArticle

Feng, L, Zhou, S, Gu, L, Gell, DA, Mackay, JP, Weiss, MJ, Gow, AJ & Shi, Y 2005, 'Structure of oxidized α-haemoglobin bound to AHSP reveals a protective mechanism for haem', Nature, vol. 435, no. 7042, pp. 697-701. https://doi.org/10.1038/nature03609
Feng L, Zhou S, Gu L, Gell DA, Mackay JP, Weiss MJ et al. Structure of oxidized α-haemoglobin bound to AHSP reveals a protective mechanism for haem. Nature. 2005 Jun 2;435(7042):697-701. https://doi.org/10.1038/nature03609
Feng, Liang ; Zhou, Suiping ; Gu, Lichuan ; Gell, David A. ; Mackay, Joel P. ; Weiss, Mitchell J. ; Gow, Andrew J. ; Shi, Yigong. / Structure of oxidized α-haemoglobin bound to AHSP reveals a protective mechanism for haem. In: Nature. 2005 ; Vol. 435, No. 7042. pp. 697-701.
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