Geometric principles in the assembly of α-helical bundles.

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.