title: Alpha-hemoglobin stabilizing protein (AHSP), a kinetic scheme of the action of a human mutant, AHSPV56G.
abstract: A kinetic analysis has been made of the interaction of alpha-Hb chains with a mutant alpha-hemoglobin stabilizing protein, AHSP(V56G), which is the first case of an AHSP mutation associated with clinical symptoms of mild thalassemia syndrome. The chaperone AHSP is thought to protect nascent alpha chains until final binding to the partner beta-Hb. Rather than protecting alpha chains, the mutant chaperone is partially unfolded but recovers its secondary structure via interaction with alpha-Hb. For both AHSP(WT) and AHSP(V56G), the binding to alpha-Hb is quite rapid relative to the alpha-beta reaction, as expected because the chaperone binding must be quite competitive to complete the alpha chain folding process before alpha-Hb binds irreversibly to beta-Hb. The main kinetic difference is a dissociation rate of AHSP(V56G).alpha-Hb some four times faster relative to AHSP.alpha-Hb. Considering a role of protein folding, the AHSP(V56G) apparently does not bind long enough (0.5 s versus 2 s for the WT) to complete the structural modifications. The overall replacement reaction (AHSP.alpha-Hb + beta-Hb --> AHSP + alphabeta) can be quite long, especially if there is an excess of AHSP relative to beta-Hb monomers.
authors.affiliation: INSERM U779, Université de Paris 7, 11 CHU Bicêtre, 78 rue du Général Leclerc, 94275 Le Kremlin-Bicêtre, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Brillet
authors.forename: Véronique
authors.initials: V
authors.lastname: Baudin-Creuza
authors.forename: Corinne
authors.initials: C
authors.lastname: Vasseur
authors.forename: Elisa
authors.initials: E
authors.lastname: Domingues-Hamdi
authors.forename: Laurent
authors.initials: L
authors.lastname: Kiger
authors.forename: Henri
authors.initials: H
authors.lastname: Wajcman
authors.forename: Serge
authors.initials: S
authors.lastname: Pissard
authors.forename: Michael C
authors.initials: MC
authors.lastname: Marden
mesh_terms: D001798:Blood Proteins / Q000737:chemistry* / Q000235:genetics*; D002248:Carbon Monoxide / Q000737:chemistry; D002648:Child; D002942:Circular Dichroism; D031541:Fluorescence Resonance Energy Transfer; D006454:Hemoglobins / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D018832:Molecular Chaperones / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D010100:Oxygen / Q000737:chemistry; D010641:Phenotype; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry; D013789:Thalassemia / Q000235:genetics
chemical_list: C468768:AHSP protein, human; D001798:Blood Proteins; D006454:Hemoglobins; D018832:Molecular Chaperones; D011994:Recombinant Proteins; D002248:Carbon Monoxide; D010100:Oxygen