Walshaw John, Woolfson Derek N
Centre for Biomolecular Design and Drug Development, John Maynard-Smith Building, School of Life Sciences, University of Sussex, Falmer BN1 9QG, UK.
J Struct Biol. 2003 Dec;144(3):349-61. doi: 10.1016/j.jsb.2003.10.014.
This year marks the 50th anniversary of Crick's seminal paper on the packing of alpha-helices into coiled-coil structures. The central tenet of Crick's work is the interdigitation of side chains, which directs the helix-helix interactions; so called knobs-into-holes packing. Subsequent determinations of coiled-coil-protein sequences and structures confirmed the key features of Crick's model and established it as a fundamental concept in structural biology. Recently, we developed a program, SOCKET, to recognise knobs-into-holes packing in protein structures, which we applied to the Protein Data Bank to compile a database of coiled-coil structures. In addition to classic structures, the database reveals 4-helix bundles and larger helical assemblies. Here, we describe how the more-complex structures can be understood by extending Crick's principles for classic coiled coils. In the simplest case, each helix of a 2-stranded structure contributes a single seam of (core) knobs-into-holes to the helical interface. 3-, 4-, and 5-Stranded structures, however, are best considered as rings of helices with cycles of knobs-into-holes. These higher-order oligomers make additional (peripheral) knobs-into-holes that broaden the helical contacts. Combinations of core and peripheral knobs may be assigned to different sequence repeats offset within the same helix. Such multiple repeats lead to multi-faceted helices, which explain structures above dimers. For instance, coiled-coil oligomer state correlates with the offset of the different repeats along a sequence. In addition, certain multi-helix assemblies can be considered as conjoined coiled coils in which multi-faceted helices participate in more than one coiled-coil motif.
今年是克里克关于α螺旋堆积形成卷曲螺旋结构的开创性论文发表50周年。克里克研究的核心原则是侧链的相互交错，它指导着螺旋-螺旋相互作用；即所谓的旋钮-入-孔堆积。随后对卷曲螺旋蛋白序列和结构的测定证实了克里克模型的关键特征，并将其确立为结构生物学的一个基本概念。最近，我们开发了一个程序SOCKET，用于识别蛋白质结构中的旋钮-入-孔堆积，我们将其应用于蛋白质数据库以编制卷曲螺旋结构数据库。除了经典结构外，该数据库还揭示了4螺旋束和更大的螺旋组装体。在这里，我们描述了如何通过扩展克里克关于经典卷曲螺旋的原理来理解更复杂的结构。在最简单的情况下，双链结构的每个螺旋为螺旋界面贡献一条（核心）旋钮-入-孔的接缝。然而，三链、四链和五链结构最好被视为具有旋钮-入-孔循环的螺旋环。这些高阶寡聚体形成额外的（外围）旋钮-入-孔，从而拓宽了螺旋接触。核心和外围旋钮的组合可以分配到同一螺旋内偏移的不同序列重复中。这种多重重复导致多面螺旋，这解释了二聚体以上的结构。例如，卷曲螺旋寡聚体状态与不同重复沿序列的偏移相关。此外，某些多螺旋组装体可以被视为连体卷曲螺旋，其中多面螺旋参与不止一个卷曲螺旋基序。
