The standard molecular model of the fiber of the sickle hemoglobin (HbS: β6 Glu → Val) has been revised to allow both β6 mutation sites to participate in intermolecular contacts, rather than only one β6 site as previously thought, for four molecules per 14-molecule fiber cross section. This structure accurately predicts the copolymerization of hybridized mixtures of HbS with HbA or HbC (β6 Glu → Lys), which could not be reconciled with prior models in which only half the β6 sites were required for assembly. This model suggests new contacts within the fiber and raises the question of whether these cross-linked double strands could possess added stability important in such processes as nucleation.
