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Published on: April 17, 2017
Dynamics of Quaternary Structure Transitions in R-State Carbonmonoxyhemoglobin Unveiled in Time-Resolved X-ray
Hyun Sun Cho1, Friedrich Schotte1, Valentyn Stadnytskyi1
1Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases , National Institutes of Health , Bethesda , Maryland 220892-0520 , United States.
Abstract:
It is well-known that tetrameric hemoglobin binds ligands cooperatively by undergoing a ligand-induced T → R quaternary structure transition, a structure-function relationship that has long served as a model system for understanding allostery in proteins. However, kinetic studies of the reverse, R → T quaternary structure transition following photolysis of carbonmonoxyhemoglobin (HbCO) reveal complex behavior that may be better explained by the presence of two different R quaternary structures coexisting in thermal equilibrium. Indeed, we report here time-resolved small- and wide-angle X-ray scattering (SAXS/WAXS) patterns of HbCO following a temperature jump that not only provide unambiguous evidence for more than one R state, but also unveil the time scale for interconversion between them. Since the time scale for the photolysis-induced R → T transition is likely different for different R-states, this structural heterogeneity must be accounted for to properly explain the kinetic heterogeneity observed in time-resolved spectroscopic studies following photolysis of HbCO.
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