School of Chemistry, National University of Ireland Galway, University Road, Galway, Ireland.
Synchrotron SOLEIL, L'Orme des Merisiers, Saint-Aubin BP48, 91192, Gif-sur-Yvette Cedex, France.
Angew Chem Int Ed Engl. 2018 Oct 15;57(42):13764-13769. doi: 10.1002/anie.201807490. Epub 2018 Sep 12.
Controlled protein assembly provides a means to regulate function. Supramolecular building blocks, including rigid macrocycles, are versatile triggers of protein assembly. Now it is shown that sulfonato-calix[8]arene (sclx ) mediates the formation of cytochrome c tetramers in solution. This tetramer spontaneously disassembles at ≥2 equivalents of sclx , providing a remarkable example of auto-regulation. Using X-ray crystallography the sclx binding sites on cytochrome c were characterized. Crystal structures at different protein-ligand ratios reveal varying degrees (up to 35 %) of protein surface coverage by the flexible calixarene and suggest a mechanism for oligomer disassembly. The solution structure of the oligomer was characterized by small-angle X-ray scattering. Overall, the data indicate calixarene-controlled protein assembly and disassembly without the requirement for a competitive inhibitor, and point to protein encapsulation by a flexible macrocycle.
控制蛋白质组装提供了一种调节功能的方法。超分子建筑块，包括刚性大环，是蛋白质组装的多功能触发物。现在已经表明，磺酸钠杯[8]芳烃（sclx）介导细胞色素 c 四聚体在溶液中的形成。这种四聚体在≥2 当量的 sclx 下自发解离，提供了一个显著的自动调节的例子。使用 X 射线晶体学，研究了细胞色素 c 上的 sclx 结合位点。在不同的蛋白质-配体比例下的晶体结构揭示了柔性杯芳烃对蛋白质表面的覆盖程度不同（高达 35%），并提出了一种寡聚体解离的机制。通过小角 X 射线散射对寡聚体的溶液结构进行了表征。总的来说，这些数据表明，杯芳烃控制的蛋白质组装和拆卸不需要竞争性抑制剂，并指出了由柔性大环对蛋白质的封装。
