AHSP (α-haemoglobin-stabilizing protein) stabilizes apo-α-haemoglobin in a partially folded state.
To produce functional Hb (haemoglobin), nascent α-globin (αo) and β-globin (βo) chains must each bind a single haem molecule (to form αh and βh) and interact together to form heterodimers. The precise sequence of binding events is unknown, and it has been suggested that additional factors might enhance the efficiency of Hb folding. AHSP (α-haemoglobin-stabilizing protein) has been shown previously to bind αh and regulate redox activity of the haem iron. In the present study, we used a combination of classical and dynamic light scattering and NMR spectroscopy to demonstrate that AHSP forms a heterodimeric complex with αo that inhibits αo aggregation and promotes αo folding in the absence of haem. These findings indicate that AHSP may function as an αo-specific chaperone, and suggest an important role for αo in guiding Hb assembly by stabilizing βo and inhibiting off-pathway self-association of βh.
Krishna Kumar
Kaavya
K
School of Molecular Bioscience, University of Sydney, Sydney, NSW 2006, Australia.
Dickson
Claire F
CF
Weiss
Mitchell J
MJ
Mackay
Joel P
JP
Gell
David A
DA
D001059:Apoproteins / Q000737:chemistry*; D001798:Blood Proteins / Q000378:metabolism*; D002942:Circular Dichroism; D019281:Dimerization; D004355:Drug Stability; D006441:Hemoglobin A / Q000737:chemistry / Q000378:metabolism; D006454:Hemoglobins / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry*; D011489:Protein Denaturation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry; D012542:Scattering, Radiation; D012995:Solubility; D013816:Thermodynamics
C468768:AHSP protein, human; D001059:Apoproteins; D001798:Blood Proteins; D006454:Hemoglobins; D018832:Molecular Chaperones; D010446:Peptide Fragments; D021122:Protein Subunits; C023478:apohemoglobin; C070077:alpha(A) globin; D006441:Hemoglobin A