Molecular topology in crystals and fibers of hemoglobin S |
| |
Authors: | Stuart J. Edelstein |
| |
Affiliation: | Section of Biochemistry, Molecular and Cell Biology Division of Biological Sciences Cornell University, Ithaca, NY 14853, U.S.A. |
| |
Abstract: | Several lines of evidence indicate a close correspondence between the linear double filaments in the crystal form of hemoglobin S grown from solutions containing polyethylene glycol and the seven pairs of helical filaments that occur in the 14-filament fibers of hemoglobin S. An analysis of the adjustments to the intermolecular contacts required to convert the double filaments from crystals to fibers is presented here. In addition, postulated contacts between the helical double filaments, which are distinct from any of the contacts of the crystals, are specified for the first time. The movements from crystals to fibers are described in terms of three rotation angles: α, the inclination of the filaments with respect to the fiber axis; δ, the tilt of successive molecules along the filaments; and ω, the rotation of successive molecules along the filaments. On the basis of the fiber structure determined by three-dimensional reconstruction of electron micrographs and the assignment of filament pairs from data on incomplete fibers, the various angles have been evaluated. For the filaments at various radii in the fibers, a varies from 3 ° to 12 °, δ varies from 1 ° to 4 ° and ω is constant at 9 °. The effects of the rotations on the contacts between molecules of hemoglobin S at various positions in the fibers are characterized using surface maps based on polar coordinates. For each residue on the surface of hemoglobin the centroid position of its side-chain is located by a longitude, a latitude and an altitude. Locations on the maps are assigned for the contacts within the helical double filaments, as well as 11 classes of new contacts describing the potential interaction sites between double filaments. The resulting maps (1) deduce roles for the various α mutants of hemoglobin known to influence fiber formation that have been identified by the Benesches; (2) distinguish effects for the α chain mutants on the same (cis) or opposite (trans) α1β1 dimer as the β6 Val in asymmetric tetramers; (3) propose new sites where effects of mutations on fiber formation may be found; and (4) suggest why some mutants may inhibit, while others enhance, fiber formation. Concerning the last point, the possibility of certain mutants “correcting” the effects of other mutants is proposed as a test of contact assignments. |
| |
Keywords: | |
本文献已被 ScienceDirect 等数据库收录! |
|