A Plausible Molecular Model for the 14-Filament Fibers of Sickle Cell Hemoglobin

Abstract

Image reconstruction of electron micrographs of negatively strained fibers of sickle cell hemoglobin has revealed a 14-filament structure composed of 10 outer filaments surrounding a 4-filament core. Degenerate forms of the fibers have also been characterized which lack specific pairs of filaments, implying an organization of the filaments in 7 pairs: a central pair of filaments surrounded by six peripheral pairs. The published evidence for the 14-filament structure and the specific pairing scheme2 is reviewed and related to data from other sources, particularly X-ray diffraction observations and findings on mutations at various sites on the surface of the hemoglobin molecule that influence fiber formation. On the basis of the available information and deductions from the disposition of the 7 pairs of filaments in the fibers, a molecular model of the fibers is proposed. This model places the hemoglobin S molecules, which are staggered by about one-half a molecular diameter in the 7 pairs of filaments of the fibers, in an arrangement similar to the orientation described for crystals of hemoglobin S in which molecules also occur in pairs of half-staggered strands.8 The arrangement of filament pairs in the molecular model of the fibers includes assignment of the polarity of the central pair of filaments and two specific peripheral pairs of filaments in an antiparallel orientation with respect to the remaining four pairs of filaments. Predictions of this model concerning the portions of the hemoglobin surface at various intermolecular contacts are described, involving positions α47, α75, α78 and β95 at particular interfaces between filament pairs.