血红蛋白
血红素
生物
组氨酸
珠蛋白
生物物理学
生物化学
血浆蛋白结合
结晶学
化学
氨基酸
酶
作者
Liang Feng,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
出处
期刊:Cell
[Elsevier]
日期:2004-11-01
卷期号:119 (5): 629-640
被引量:141
标识
DOI:10.1016/j.cell.2004.11.025
摘要
Hemoglobin A (HbA), the oxygen delivery system in humans, comprises two α and two β subunits. Free α-hemoglobin (αHb) is unstable, and its precipitation contributes to the pathophysiology of β thalassemia. In erythrocytes, the α-hemoglobin stabilizing protein (AHSP) binds αHb and inhibits its precipitation. The crystal structure of AHSP bound to Fe(II)-αHb reveals that AHSP specifically recognizes the G and H helices of αHb through a hydrophobic interface that largely recapitulates the α1-β1 interface of hemoglobin. The AHSP-αHb interactions are extensive but suboptimal, explaining why β-hemoglobin can competitively displace AHSP to form HbA. Remarkably, the Fe(II)-heme group in AHSP bound αHb is coordinated by the distal but not the proximal histidine. Importantly, binding to AHSP facilitates the conversion of oxy-αHb 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 αHb.
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