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

Результат исследований: Материалы для журналаСтатья

87 Цитирования (Scopus)

Аннотация

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.

Язык оригиналаАнглийский
Страницы (с-по)697-701
Число страниц5
ЖурналNature
Том435
Номер выпуска7042
DOI
СостояниеОпубликовано - 2 июн 2005
Опубликовано для внешнего пользованияДа

ASJC Scopus subject areas

  • General

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  • Цитировать

    Feng, L., Zhou, S., Gu, L., Gell, D. A., Mackay, J. P., Weiss, M. J., Gow, A. 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