| Literature DB >> 15550245 |
Liang Feng1, David A Gell, Suiping Zhou, Lichuan Gu, Yi Kong, Jianqing Li, Min Hu, Nieng Yan, Christopher Lee, Anne M Rich, Robert S Armstrong, Peter A Lay, Andrew J Gow, Mitchell J Weiss, Joel P Mackay, Yigong Shi.
Abstract
Hemoglobin A (HbA), the oxygen delivery system in humans, comprises two alpha and two beta subunits. Free alpha-hemoglobin (alphaHb) is unstable, and its precipitation contributes to the pathophysiology of beta thalassemia. In erythrocytes, the alpha-hemoglobin stabilizing protein (AHSP) binds alphaHb and inhibits its precipitation. The crystal structure of AHSP bound to Fe(II)-alphaHb reveals that AHSP specifically recognizes the G and H helices of alphaHb through a hydrophobic interface that largely recapitulates the alpha1-beta1 interface of hemoglobin. The AHSP-alphaHb interactions are extensive but suboptimal, explaining why beta-hemoglobin can competitively displace AHSP to form HbA. Remarkably, the Fe(II)-heme group in AHSP bound alphaHb is coordinated by the distal but not the proximal histidine. Importantly, binding to AHSP facilitates the conversion of oxy-alphaHb to a deoxygenated, oxidized [Fe(III)], nonreactive form in which all six coordinate positions are occupied. These observations reveal the molecular mechanisms by which AHSP stabilizes free alphaHb.Entities:
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Year: 2004 PMID： 15550245 DOI： 10.1016/j.cell.2004.11.025
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582