School of Chemistry, University of Bristol, Bristol, UK.
Department of Chemical and Structural Biology, Weizmann Institute of Science, Rehovot, Israel.
Protein Sci. 2023 Nov;32(11):e4789. doi: 10.1002/pro.4789.
α-Helical coiled coils are common tertiary and quaternary elements of protein structure. In coiled coils, two or more α helices wrap around each other to form bundles. This apparently simple structural motif can generate many architectures and topologies. Coiled coil-forming sequences can be predicted from heptad repeats of hydrophobic and polar residues, hpphppp, although this is not always reliable. Alternatively, coiled-coil structures can be identified using the program SOCKET, which finds knobs-into-holes (KIH) packing between side chains of neighboring helices. SOCKET also classifies coiled-coil architecture and topology, thus allowing sequence-to-structure relationships to be garnered. In 2009, we used SOCKET to create a relational database of coiled-coil structures, CC , from the RCSB Protein Data Bank (PDB). Here, we report an update of CC following an update of SOCKET (to Socket2) and the recent explosion of structural data and the success of AlphaFold2 in predicting protein structures from genome sequences. With the most-stringent SOCKET parameters, CC contains ≈12,000 coiled-coil assemblies from experimentally determined structures, and ≈120,000 potential coiled-coil structures within single-chain models predicted by AlphaFold2 across 48 proteomes. CC allows these and other less-stringently defined coiled coils to be searched at various levels of structure, sequence, and side-chain interactions. The identified coiled coils can be viewed directly from CC using the Socket2 application, and their associated data can be downloaded for further analyses. CC is available freely at http://coiledcoils.chm.bris.ac.uk/CCPlus/Home.html. It will be updated automatically. We envisage that CC+ could be used to understand coiled-coil assemblies and their sequence-to-structure relationships, and to aid protein design and engineering.
α-螺旋卷曲螺旋是蛋白质结构的常见三级和四级元件。在卷曲螺旋中，两个或更多的α螺旋相互缠绕形成束。这个明显简单的结构基元可以产生许多结构和拓扑结构。卷曲螺旋形成序列可以从疏水性和亲水性残基的七肽重复 hpphppp 预测，尽管这并不总是可靠的。或者，可以使用程序 SOCKET 识别卷曲螺旋结构，该程序在相邻螺旋的侧链之间找到旋钮孔（KIH）包装。SOCKET 还对卷曲螺旋结构进行分类和拓扑结构，从而可以获得序列-结构关系。 2009 年，我们使用 SOCKET 从 RCSB 蛋白质数据库（PDB）创建了卷曲螺旋结构的关系数据库 CC。在这里，我们报告了 SOCKET 更新（至 Socket2）以及结构数据最近爆炸式增长和 AlphaFold2 从基因组序列预测蛋白质结构成功之后 CC 的更新。使用最严格的 SOCKET 参数，CC 包含来自实验确定结构的约 12000 个卷曲螺旋组装体和约 120000 个潜在卷曲螺旋结构，这些结构是通过 AlphaFold2 在 48 个蛋白质组中预测的单链模型产生的。CC 允许在各种结构、序列和侧链相互作用级别上搜索这些和其他定义不那么严格的卷曲螺旋。可以使用 Socket2 应用程序直接从 CC 查看已识别的卷曲螺旋，并且可以下载它们的相关数据以进行进一步分析。CC 可免费在 http://coiledcoils.chm.bris.ac.uk/CCPlus/Home.html 获得。它将自动更新。我们设想 CC+可以用于理解卷曲螺旋组装及其序列-结构关系，并辅助蛋白质设计和工程。
