The sickling variant of human hemoglobin, Hb S (beta 6 Glu-->Val), assembles into 14-strand helical fibers composed of seven pairs of double strands. The organization of the helical double strands closely resembles the parallel, half-staggered, linear strand pairs of the crystals of Hb S characterized by Wishner et al. In the crystals, the molecules are arranged such that each possesses a beta 6 Val in contact with a molecule on the opposite strand. In the fibers, the overall hexagonal packing of strands leads to 22 classes of potential contacts between the seven double strands, but the presence of 2-fold helical symmetry reduces these contacts to 11 distinct classes. An analysis of the intermolecular contacts reported by Watowich et al., based on the data of Carragher et al., indicated a loosely packed structure for which only four of the 11 potential classes of contacts between double strands are significant (residues within 5 A). We have recently analyzed the packing based on the results of Dykes et al. and Rodgers et al., and compared the findings with the structure derived from the data of Carragher et al. We find serious differences between the two data sets concerning the packing of double strands. The Dykes-Rodgers data indicate a more closely packed structure in which nine of the 11 potential classes of contacts are within 5 A. Considerations on the stability of certain contacts derived from incomplete fibers, as well as studies of Hb molecules composed of beta S chains and mutant alpha chains, suggest that the structural model with closer packing of the double strands provides a better correlation with the other experimental results.
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