Protein Frameworks with Thiacalixarene and Zinc

Area of Science:

• Supramolecular Chemistry
• Biomaterials Science
• Protein Engineering

Background:

• Controlled protein assembly is crucial for creating novel biomaterials.
• Synthetic macrocycles, like sulfonato-calix[n]arenes, can mediate protein assembly.
• Sulfonato-thiacalix[4]arene (tsclx) possesses metal-binding capabilities for dual-mediated assembly.

Purpose of the Study:

• To investigate the tsclx-/Zn-directed assembly of two distinct proteins: cytochrome c (cyt c) and Ralstonia solanacearum lectin (RSL).
• To explore the role of tsclx conformation and metal coordination in protein-protein interactions.

Main Methods:

• Co-crystallization of tsclx/Zn complexes with cyt c and RSL.
• Structural analysis of the resulting protein-macrocycle-metal assemblies.
• Characterization of assembly mechanisms involving encapsulation and metal coordination.

Main Results:

• Two co-crystal forms of cyt c were obtained, featuring multinuclear zinc sites stabilized by the cone conformation of tsclx.
• The tsclx/Zn cluster mediated cyt c assembly through lysine encapsulation and protein-protein contacts.
• For RSL, tsclx adopted a 1,2-alternate conformation, supporting a dinuclear zinc site that bound histidine residues.

Conclusions:

• Tsclx/Zn complexes effectively direct the assembly of different proteins via macrocycle and metal interactions.
• The conformational flexibility of tsclx influences the assembly outcome and metal coordination.
• These findings highlight the potential of thiacalixarenes in fabricating advanced biomaterials and metal-organic frameworks (MOFs).