Auto-regulated Protein Assembly on a Supramolecular Scaffold

Area of Science:

• Biochemistry
• Supramolecular Chemistry
• Structural Biology

Background:

• Controlled protein assembly is crucial for regulating biological functions.
• Supramolecular building blocks, such as macrocycles, can act as versatile triggers for protein assembly.

Purpose of the Study:

• To investigate the role of sulfonato-calix[8]arene (sclx8) in mediating the assembly of cytochrome c.
• To elucidate the mechanism of sclx8-induced protein assembly and disassembly.

Main Methods:

• X-ray crystallography was used to characterize sclx8 binding sites on cytochrome c.
• Small-angle X-ray scattering (SAXS) was employed to determine the solution structure of the protein oligomer.

Main Results:

• Sulfonato-calix[8]arene (sclx8) mediates the formation of cytochrome c tetramers in solution.
• The tetramer spontaneously disassembles at higher sclx8 concentrations (≥2 equivalents), demonstrating auto-regulation.
• Crystal structures revealed varying protein surface coverage by sclx8, suggesting a disassembly mechanism.

Conclusions:

• Flexible macrocycles like sclx8 can control protein assembly and disassembly dynamically.
• Protein encapsulation by macrocycles offers a novel strategy for regulating protein function without competitive inhibitors.