Aggregation of deoxyhemoglobin S at low concentrations.

Area of Science:

• Biochemistry
• Molecular Biology
• Hematology

Background:

• Hemoglobin S (Hb S) is known to polymerize under deoxygenated conditions.
• Understanding the initial steps of deoxy-Hb S self-association is crucial for comprehending sickle cell disease pathogenesis.

Purpose of the Study:

• To quantify the self-association of deoxyhemoglobin S in dilute solutions.
• To investigate the concentration-dependent behavior of oxy- and deoxy-Hb S.

Main Methods:

• Rayleigh light scattering at 630 nm.
• Osmometry in 0.05 M potassium phosphate buffer (pH 7.35).
• Determination of weight and number average molecular weights (Mw and Mn) and virial coefficients (B').

Main Results:

• No significant differences between oxy- and deoxy-Hb S molecular weights below 2 g/dl.
• Above 2 g/dl, Mn and Mw of deoxy-Hb S significantly differed from oxy-Hb S.
• A negative second virial coefficient for deoxy-Hb S indicated self-association.
• Propylurea had no effect, while NaCl influenced aggregation, suggesting polar interactions.

Conclusions:

• Deoxyhemoglobin S undergoes concentration-dependent self-association in dilute solutions.
• Polar interactions play a significant role in the formation of deoxy-Hb S aggregates.
• These findings provide insights into the molecular mechanisms underlying hemoglobinopathies.