1XZY
Solution structure of the P30-trans form of Alpha Hemoglobin Stabilizing Protein (AHSP)
Summary for 1XZY
| Entry DOI | 10.2210/pdb1xzy/pdb |
| Related | 1W09 1W0A 1W0B |
| Descriptor | Alpha-hemoglobin stabilizing protein (1 entity in total) |
| Functional Keywords | helical bundle, three-helix bundle, chaperone |
| Biological source | Homo sapiens (human) |
| Cellular location | Cytoplasm: Q9NZD4 |
| Total number of polymer chains | 1 |
| Total formula weight | 10597.03 |
| Authors | Gell, D.A.,Feng, L.,Zhou, S.,Kong, Y.,Lee, C.,Weiss, M.J.,Shi, Y.,Mackay, J.P. (deposition date: 2004-11-12, release date: 2004-12-21, Last modification date: 2024-05-29) |
| Primary citation | Feng, L.,Gell, D.A.,Zhou, S.,Gu, L.,Kong, Y.,Li, J.,Hu, M.,Yan, N.,Lee, C.,Rich, A.M.,Armstrong, R.S.,Lay, P.A.,Gow, A.J.,Weiss, M.J.,Mackay, J.P.,Shi, Y. Molecular mechanism of AHSP-mediated stabilization of alpha-hemoglobin Cell(Cambridge,Mass.), 119:629-640, 2004 Cited by PubMed 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. PubMed: 15550245DOI: 10.1016/j.cell.2004.11.025 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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