Cretegny I, Edelstein S J
Department of Biochemistry, University of Geneva, Switzerland.
J Mol Biol. 1993 Apr 5;230(3):733-8. doi: 10.1006/jmbi.1993.1195.
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.
人类血红蛋白的镰状变体Hb S（β6谷氨酸→缬氨酸）组装成由七对双链组成的14链螺旋纤维。螺旋双链的结构与Wishner等人所描述的Hb S晶体的平行、半交错、线性链对非常相似。在晶体中，分子排列方式使得每个分子的β6缬氨酸与相反链上的一个分子接触。在纤维中，链的整体六边形堆积导致七对双链之间有22种潜在接触，但由于存在二重螺旋对称性，这些接触减少到11种不同类型。基于Carragher等人的数据，对Watowich等人报道的分子间接触进行分析，结果表明其结构松散，双链间11种潜在接触类型中只有四种（5埃以内的残基）是显著的。我们最近根据Dykes等人和Rodgers等人的结果分析了堆积情况，并将结果与从Carragher等人的数据得出的结构进行了比较。我们发现这两组数据在双链堆积方面存在严重差异。Dykes-Rodgers的数据表明结构堆积更紧密，11种潜在接触类型中有九种在5埃以内。对来自不完整纤维的某些接触稳定性的考虑，以及对由βS链和突变α链组成的Hb分子的研究表明，双链堆积更紧密的结构模型与其他实验结果具有更好的相关性。
