Rennie Martin L, Crowley Peter B
School of Chemistry, National University of Ireland Galway, University Road, Galway, Ireland.
Present address: Institute of Molecular Cell and System Biology, University of Glasgow, University Avenue, Glasgow, UK.
Chemphyschem. 2019 Apr 16;20(8):1011-1017. doi: 10.1002/cphc.201900153. Epub 2019 Mar 28.
Ligand-mediated regulation of protein assembly occurs frequently in different cellular contexts. Auto-regulated assembly, where a ligand acts as its own competitive inhibitor, provides a mechanism for exquisite control of assembly. Unlike simple protein-ligand systems a quantification of the binding thermodynamics is not straightforward. Here, we characterize the interactions of a recently identified model system in which the oligomerization of cytochrome c is controlled by sulfonato-calix[8]arene, an anionic supramolecular scaffold. Isothermal titration calorimetry and thermodynamic modelling, in combination with Bayesian fitting, were used to quantify the ligand binding and assembly equilibria for this system. The approach and variations of this model may prove useful for the analysis of auto-regulated protein assembly in general.
配体介导的蛋白质组装调控在不同的细胞环境中频繁发生。自调控组装中，配体作为自身的竞争性抑制剂，提供了一种精确控制组装的机制。与简单的蛋白质-配体系统不同，结合热力学的量化并非易事。在此，我们表征了一个最近鉴定出的模型系统的相互作用，其中细胞色素c的寡聚化由磺基杯[8]芳烃（一种阴离子超分子支架）控制。等温滴定量热法和热力学建模，结合贝叶斯拟合，用于量化该系统的配体结合和组装平衡。该模型的方法及变体可能总体上对自调控蛋白质组装的分析有用。
