Auto-regulated Protein Assembly on a Supramolecular Scaffold.
Rennie, M.L., Fox, G.C., Perez, J., Crowley, P.B.(2018) Angew Chem Int Ed Engl 57: 13764-13769
- PubMed: 30109907 
- DOI: https://doi.org/10.1002/anie.201807490
- Primary Citation of Related Structures:  
6GD6, 6GD7, 6GD8, 6GD9 - PubMed Abstract: 
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 8 ) mediates the formation of cytochrome c tetramers in solution. This tetramer spontaneously disassembles at ≥2 equivalents of sclx 8 , providing a remarkable example of auto-regulation. Using X-ray crystallography the sclx 8 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.
Organizational Affiliation: 
School of Chemistry, National University of Ireland Galway, University Road, Galway, Ireland.