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Biophys J, August 2002, p. 1147-1156, Vol. 83, No. 2
¶
§ and¶
*Department of Chemical Engineering, University of Houston,
Houston, Texas 77204; Center for Microgravity and
Materials Research, University of Alabama in Huntsville, Huntsville,
Alabama 35899; the Departments of Medicine (Division of
Hematology), §Physiology and Biophysics, and
¶Anatomy and Structural Biology, Albert Einstein College
of Medicine and Montefiore Hospital, Comprehensive Sickle Cell Center,
The Bronx, New York 10461 USA
The mutated hemoglobin HbC (
6 Glu
Lys), in the
oxygenated (R) liganded state, forms crystals inside red blood cells of
patients with CC and SC diseases. Static and dynamic light scattering
characterization of the interactions between the R-state (CO) HbC, HbA,
and HbS molecules in low-ionic-strength solutions showed that
electrostatics is unimportant and that the interactions are dominated
by the specific binding of solutions' ions to the proteins.
Microscopic observations and determinations of the nucleation
statistics showed that the crystals of HbC nucleate and grow by the
attachment of native molecules from the solution and that concurrent
amorphous phases, spherulites, and microfibers are not building blocks
for the crystal. Using a novel miniaturized light-scintillation
technique, we quantified a strong retrograde solubility dependence on
temperature. Thermodynamic analyses of HbC crystallization yielded a
high positive enthalpy of 155 kJ mol
1, i.e., the specific
interactions favor HbC molecules in the solute state. Then, HbC
crystallization is only possible because of the huge entropy gain of
610 J mol1 K1, likely stemming from the
release of up to 10 water molecules per protein intermolecular
contact
hydrophobic interaction. Thus, the higher crystallization
propensity of R-state HbC is attributable to increased hydrophobicity
resulting from the conformational changes that accompany the HbC 6 mutation.
Biophys J, August 2002, p. 1147-1156, Vol. 83, No. 2
© 2002 by the Biophysical Society 0006-3495/02/08/1147/10 $2.00
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