A Thermodynamic Model of Auto‐regulated Protein Assembly by a Supramolecular Scaffold. Issue 8 (28th March 2019)

• Record Type: Journal Article
• Authors: Rennie, Martin L.; Crowley, Peter B.
• Is Part Of: Chemphyschem. Volume 20:Issue 8(2019)
• Page Start: 1011
• Page End: 1017
• Publication Date: 2019-03-28
• Subjects: Bayesian fitting -- calix[8]arene -- cytochrome c -- multi-body -- oligomerization; Chemistry, Physical and theoretical -- Periodicals; 541.05
• DOI: 10.1002/cphc.201900153
• Languages: English
• ISSNs: 1439-4235

Abstract

Abstract: 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. Abstract : Auto‐regulated assembly of cytochrome c by sulfonato‐calix[8]arene results in biphasic isothermal titration calorimetry (ITC) thermograms. The interpretation of such data is non‐trivial. The authors quantified the thermodynamics of ligand binding and assembly by testing several models with Bayesian fitting. Simultaneous data fitting to standard and reverse titrations was performed. Variations of the model may aid the analysis of auto‐regulated assembly in general.