ArticleThe Journal of biological chemistry2012
Kinetics of α-globin binding to α-hemoglobin stabilizing protein (AHSP) indicate preferential stabilization of hemichrome folding intermediate.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Review
- The role of globins in cardiovascular physiology.Physiological reviews · 2022Review
- Redox-Regulation of α-Globin in Vascular Physiology.Antioxidants (Basel, Switzerland) · 2022Article
- The Hsp70 chaperone system: distinct roles in erythrocyte formation and maintenance.Haematologica · 2021Review
- The Interplay between Molten Globules and Heme Disassociation Defines Human Hemoglobin Disassembly.Biophysical journal · 2020Article
- Alpha-hemoglobin-stabilizing protein (AHSP): a modulatory factor in β-thalassemia.International journal of hematology · 2020Review
- Endothelial cell α-globin and its molecular chaperone α-hemoglobin-stabilizing protein regulate arteriolar contractility.The Journal of clinical investigation · 2018Article
- Replacement of the Distal Histidine Reveals a Noncanonical Heme Binding Site in a 2-on-2 Hemoglobin.Biochemistry · 2018Article
- The structure of α-haemoglobin in complex with a haemoglobin-binding domain from Staphylococcus aureus reveals the elusive α-haemoglobin dimerization interface.Acta crystallographica. Section F, Structural biology communications · 2014Article
- α-Hemoglobin-stabilizing protein (AHSP) perturbs the proximal heme pocket of oxy-α-hemoglobin and weakens the iron-oxygen bond.The Journal of biological chemistry · 2013Article
- Hemoglobin variants: biochemical properties and clinical correlates.Cold Spring Harbor perspectives in medicine · 2013Review
- α-Hemoglobin stabilizing protein (AHSP) markedly decreases the redox potential and reactivity of α-subunits of human HbA with hydrogen peroxide.The Journal of biological chemistry · 2013Article
- Classification of the disorders of hemoglobin.Cold Spring Harbor perspectives in medicine · 2013Review
- Do not super-excess me!Blood · 2012Article
- Insights into hemoglobin assembly through in vivo mutagenesis of α-hemoglobin stabilizing protein.The Journal of biological chemistry · 2012Article
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Authors and funding
4 authors.
Funding
Abstract
Human α-hemoglobin stabilizing protein (AHSP) is a conserved mammalian erythroid protein that facilitates the production of Hemoglobin A by stabilizing free α-globin. AHSP rapidly binds to ferrous α with association (k'(AHSP)) and dissociation (k(AHSP)) rate constants of ≈10 μm(-1) s(-1) and 0.2 s(-1), respectively, at pH 7.4 at 22 °C. A small slow phase was observed when AHSP binds to excess ferrous αCO. This slow phase appears to be due to cis to trans prolyl isomerization of the Asp(29)-Pro(30) peptide bond in wild-type AHSP because it was absent when αCO was mixed with P30A and P30W AHSP, which are fixed in the trans conformation. This slow phase was also absent when met(Fe(3+))-α reacted with wild-type AHSP, suggesting that met-α is capable of rapidly binding to either Pro(30) conformer. Both wild-type and Pro(30)-substituted AHSPs drive the formation of a met-α hemichrome conformation following binding to either met- or oxy(Fe(2+))-α. The dissociation rate of the met-α·AHSP complex (k(AHSP) ≈ 0.002 s(-1)) is ∼100-fold slower than that for ferrous α·AHSP complexes, resulting in a much higher affinity of AHSP for met-α. Thus, in vivo, AHSP acts as a molecular chaperone by rapidly binding and stabilizing met-α hemichrome folding intermediates. The low rate of met-α dissociation also allows AHSP to have a quality control function by kinetically trapping ferric α and preventing its incorporation into less stable mixed valence Hemoglobin A tetramers. Reduction of AHSP-bound met-α allows more rapid release to β subunits to form stable fully, reduced hemoglobin dimers and tetramers.
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