Walshaw J, Woolfson D N
Centre for Biomolecular Design and Drug Development, School of Biological Sciences, University of Sussex, Falmer BN1 9QG, UK.
Protein Sci. 2001 Mar;10(3):668-73. doi: 10.1110/ps.36901.
The coiled coil is a ubiquitous protein-folding motif. It generally is accepted that coiled coils are characterized by sequence patterns known as heptad repeats. Such patterns direct the formation and assembly of amphipathic alpha-helices, the hydrophobic faces of which interface in a specific manner first proposed by Crick and termed "knobs-into-holes packing". We developed software, SOCKET, to recognize this packing in protein structures. As expected, in a trawl of the protein data bank, we found examples of canonical coiled coils with a single contiguous heptad repeat. In addition, we identified structures with multiple, overlapping heptad repeats. This observation extends Crick's original postulate: Multiple, offset heptad repeats help explain assemblies with more than two helices. Indeed, we have found that the sequence offset of the multiple heptad repeats is related to the coiled-coil oligomer state. Here we focus on one particular sequence motif in which two heptad repeats are offset by two residues. This offset sets up two hydrophobic faces separated by approximately 150 degrees -160 degrees around the alpha-helix. In turn, two different combinations of these faces are possible. Either similar or opposite faces can interface, which leads to open or closed multihelix assemblies. Accordingly, we refer to these two forms as alpha-sheets and alpha-cylinders. We illustrate these structures with our own predictions and by reference to natural variants on these designs that have recently come to light.
卷曲螺旋是一种普遍存在的蛋白质折叠基序。人们普遍认为，卷曲螺旋的特征在于被称为七肽重复序列的序列模式。这些模式指导两亲性α螺旋的形成和组装，其疏水面以一种由克里克首次提出并称为“旋钮入孔堆积”的特定方式相互作用。我们开发了软件SOCKET来识别蛋白质结构中的这种堆积。正如预期的那样，在对蛋白质数据库的搜索中，我们发现了具有单个连续七肽重复序列的典型卷曲螺旋的例子。此外，我们还鉴定出了具有多个重叠七肽重复序列的结构。这一观察结果扩展了克里克最初的假设：多个错开的七肽重复序列有助于解释具有两个以上螺旋的组装体。事实上，我们发现多个七肽重复序列的序列偏移与卷曲螺旋的寡聚状态有关。在这里，我们关注一种特定的序列基序，其中两个七肽重复序列错开两个残基。这种偏移在α螺旋周围形成了两个相隔约150度-160度的疏水面。反过来，这些面有两种不同的组合方式。相似或相对的面都可以相互作用，这会导致开放或封闭的多螺旋组装体。因此，我们将这两种形式称为α片层和α圆柱体。我们通过自己的预测以及参考最近发现的这些设计的天然变体来说明这些结构。
