Guelph-Waterloo Centre for Graduate Studies in Chemistry and Biochemistry, University of Waterloo, 200 University Avenue West, Waterloo, Ontario, N2L 3G1, Canada.
Structure. 2012 Jan 11;20(1):161-71. doi: 10.1016/j.str.2011.10.021. Epub 2011 Dec 15.
The high frequency of internal structural symmetry in common protein folds is presumed to reflect their evolutionary origins from the repetition and fusion of ancient peptide modules, but little is known about the primary sequence and physical determinants of this process. Unexpectedly, a sequence and structural analysis of symmetric subdomain modules within an abundant and ancient globular fold, the β-trefoil, reveals that modular evolution is not simply a relic of the ancient past, but is an ongoing and recurring mechanism for regenerating symmetry, having occurred independently in numerous existing β-trefoil proteins. We performed a computational reconstruction of a β-trefoil subdomain module and repeated it to form a newly three-fold symmetric globular protein, ThreeFoil. In addition to its near perfect structural identity between symmetric modules, ThreeFoil is highly soluble, performs multivalent carbohydrate binding, and has remarkably high thermal stability. These findings have far-reaching implications for understanding the evolution and design of proteins via subdomain modules.
常见蛋白质折叠结构中高度的内部结构对称性被认为反映了它们从古老肽模块的重复和融合进化而来，但对于这一过程的原始序列和物理决定因素知之甚少。出乎意料的是，对丰富而古老的球状折叠结构（β-三叶形）中的对称亚结构模块的序列和结构分析表明，模块进化不仅仅是古老过去的遗迹，而是一种正在进行并经常发生的机制，用于再生对称性，这种机制在许多现有的β-三叶形蛋白中独立发生。我们对β-三叶形亚结构模块进行了计算重建，并对其进行重复以形成新的具有三重对称的球状蛋白质 ThreeFoil。除了对称模块之间几乎完美的结构一致性外，ThreeFoil 还具有很高的可溶性、多价碳水化合物结合能力和非常高的热稳定性。这些发现对于通过亚结构模块理解蛋白质的进化和设计具有深远的意义。
