The structural link between polymerization and sickle cell disease.

Abstract

Sickle hemoglobin molecules assemble into polymers composed of seven helically twisted double strands. Intermolecular contacts involving the mutation sites within the double strands are well established. We show that the same contact sites are present at the polymer surface on four of the ten exterior molecules in each layer, and demonstrate that the identical contact geometry can be achieved between polymers as found within the double strands. This provides a structural rationale for the exponential rate of polymer growth that characterizes the kinetics of gelation. This also gives a structural basis for the cross-linking which solidifies the polymer gel. In the absence of these surface contact regions sickle cell disease would be a much milder syndrome.