Molecular and Structural Biology Division, Central Drug Research Institute, 10/1 Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226 020, India.
Philos Trans A Math Phys Eng Sci. 2013 May 20;371(1993):20120369. doi: 10.1098/rsta.2012.0369. Print 2013 Jun 28.
α-Helical coiled coils are usually stabilized by hydrophobic interfaces between the two constituent α-helices, in the form of 'knobs-into-holes' packing of non-polar residues arranged in repeating heptad patterns. Here we examine the corresponding 'hydrophobic cores' that stabilize bundles of four α-helices. In particular, we study three different kinds of bundle, involving four α-helices of identical sequence: two pack in a parallel and one in an anti-parallel orientation. We point out that the simplest way of understanding the packing of these 4-helix bundles is to use Crick's original idea that the helices are held together by 'hydrophobic stripes', which are readily visualized on the cylindrical surface lattice of the α-helices; and that the 'helix-crossing angle'--which determines, in particular, whether supercoiling is left- or right-handed--is fixed by the slope of the lattice lines that contain the hydrophobic residues. In our three examples the constituent α-helices have hydrophobic repeat patterns of 7, 11 and 4 residues, respectively; and we associate the different overall conformations with 'knobs-into-holes' packing along the 7-, 11- and 4-start lines, respectively, of the cylindrical surface lattices of the constituent α-helices. For the first two examples, all four interfaces between adjacent helices are geometrically equivalent; but in the third, one of the four interfaces differs significantly from the others. We provide a geometrical explanation for this non-equivalence in terms of two different but equivalent ways of assembling this bundle, which may possibly constitute a bistable molecular 'switch' with a coaxial throw of about 12 Å. The geometrical ideas that we deploy in this paper provide the simplest and clearest description of the structure of helical bundles. In an appendix, we describe briefly a computer program that we have devised in order to search for 'knobs-into-holes' packing between α-helices in proteins.
α-螺旋卷曲螺旋通常通过两个组成α-螺旋之间的疏水界面稳定，形式为非极性残基以重复七肽模式排列的“旋钮入孔”包装。在这里，我们研究了稳定四个α-螺旋束的相应“疏水核心”。特别是，我们研究了三种不同类型的束，涉及四个相同序列的α-螺旋：两个以平行方式包装，一个以反平行方式包装。我们指出，理解这些 4 螺旋束包装的最简单方法是使用克里克的原始想法，即螺旋通过“疏水条纹”结合在一起，这些条纹在α-螺旋的圆柱面晶格上很容易可视化；并且“螺旋交叉角”——它决定了超螺旋是左手还是右手——由包含疏水残基的晶格线的斜率固定。在我们的三个例子中，组成α-螺旋的疏水重复图案分别为 7、11 和 4 个残基；我们将不同的整体构象与圆柱面晶格的 7、11 和 4 个起始线的“旋钮入孔”包装相关联组成α-螺旋。对于前两个例子，相邻螺旋之间的所有四个界面在几何上都是等效的；但在第三个例子中，四个界面之一与其他界面有很大的不同。我们根据组装此束的两种不同但等效的方法，从几何角度解释了这种非等效性，这可能构成了一个具有约 12 Å 同轴投掷的双稳态分子“开关”。我们在本文中部署的几何思想为螺旋束的结构提供了最简单和最清晰的描述。在附录中，我们简要描述了我们设计的一个计算机程序，以便在蛋白质中搜索α-螺旋之间的“旋钮入孔”包装。
