1Y01

Crystal structure of AHSP bound to Fe(II) alpha-hemoglobin

Summary for 1Y01

• Entry DOI: 10.2210/pdb1y01/pdb
• Descriptor: Alpha-hemoglobin stabilizing protein, Hemoglobin alpha chain, PROTOPORPHYRIN IX CONTAINING FE, ... (6 entities in total)
• Functional Keywords: ahsp, alpha hemoglobin, stabilization of alpha hemoglobin, hemoglobin oxidation and precipitation, recognition, oxygen storage-transport complex, oxygen storage/transport
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: Q9NZD4
• Total number of polymer chains: 2
• Total formula weight: 28105.78

Authors

Feng, L.,Gell, D.A.,Zhou, S.,Gu, L.,Gow, A.J.,Weiss, M.J.,Mackay, J.P.,Shi, Y. (deposition date: 2004-11-14, release date: 2004-12-21, Last modification date: 2024-02-14)

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

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: 15550245
DOI: 10.1016/j.cell.2004.11.025

Experimental method

X-RAY DIFFRACTION (2.8 Å)