Dynamics of α-Hb chain binding to its chaperone AHSP depends on heme coordination and redox state

摘要: Abstract Background AHSP is an erythroid molecular chaperone of the α-hemoglobin chains (α-Hb). Upon binding, native ferric α-Hb undergoes unprecedented structural rearrangement at heme site giving rise to a 6th coordination bond with His(E7). Methods Recombinant AHSP, WT α-Hb:AHSP and α-HbHE7Q:AHSP complexes were expressed in Escherichia coli. Thermal denaturation curves measured by circular dichroism for isolated bound AHSP. Kinetics ligand binding redox reactions as well release from complex time-resolved absorption spectroscopy. Results kinetically controlled prevail over direct β-chains also thermodynamically state not liganded ferrous α-Hb. The dramatic instability greatly decreased upon binding. Removing bis-histidyl hexacoordination α-HbH58(E7)Q:AHSP reduces stabilizing effect Once globin can be more easily reduced several chemical enzymatic systems compared within Hb-tetramer. Conclusion reduction could trigger its toward final Hb β-chain partner producing functional Hb-tetramers. This work indicates preferred kinetic pathway Hb-synthesis. General significance cellular balance Hb-synthesis should considered important relative proportional synthesis both Hb-subunits their cofactor. vivo role discussed context disorders observed thalassemia.