1XZY: Solution structure of the P30-trans form of Alpha Hemoglobin Stabilizing Protein (AHSP)

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.
PDB ID: 1XZYDownload
MMDB ID: 31667
PDB Deposition Date: 2004/11/12
Updated in MMDB: 2007/11
Experimental Method:
solution nmr
Source Organism:
Similar Structures:
Molecular Components in 1XZY
Label Count Molecule
Protein (1 molecule)
Alpha-hemoglobin Stabilizing Protein(Gene symbol: AHSP)
Molecule annotation
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