A thermodynamic model of auto-regulated protein assembly by a supramolecular scaffold
Rennie, Martin L.
Crowley, Peter B.
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Rennie, Martin L., & Crowley, Peter B. (2019). A Thermodynamic Model of Auto-regulated Protein Assembly by a Supramolecular Scaffold. ChemPhysChem, 20(8), 1011-1017. doi: 10.1002/cphc.201900153
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-calixarene, 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.