Watowich S J, Gross L J, Josephs R
Department of Molecular Genetics and Cell Biology, University of Chicago, IL 60637.
J Mol Biol. 1989 Oct 20;209(4):821-8. doi: 10.1016/0022-2836(89)90610-4.
By combining X-ray crystallographic co-ordinates of sickle hemoglobin (HbS) molecules with three-dimensional reconstructions of electron micrographs of HbS fibers we have synthesized a model for the structure of the clinically relevant HbS fiber. This model largely accounts for the action of 55 point mutations of HbS whose effect on fiber formation has been studied. In addition, it predicts locations at which additional point mutations are likely to affect fiber formation. The number of intermolecular axial contacts decreases with radius until, at the periphery of the fiber, there are essentially no axial contacts. We suggest that this observation accounts for the limited radial growth of the HbS fiber and that a similar mechanism may be a factor in limiting the size of other helical particles. The methodology for the synthesis of the fiber model is applicable to other systems in which X-ray crystallographic and electron microscopic data are available.
通过将镰状血红蛋白（HbS）分子的X射线晶体学坐标与HbS纤维电子显微镜照片的三维重建相结合，我们合成了一个与临床相关的HbS纤维结构模型。该模型在很大程度上解释了已研究的55个HbS点突变对纤维形成的影响。此外，它还预测了其他点突变可能影响纤维形成的位置。分子间轴向接触的数量随半径减小，直到在纤维外围基本上没有轴向接触。我们认为这一观察结果解释了HbS纤维径向生长的局限性，并且类似的机制可能是限制其他螺旋颗粒大小的一个因素。纤维模型的合成方法适用于其他可获得X射线晶体学和电子显微镜数据的系统。
