Constructing protein polyhedra via orthogonal chemical interactions

Area of Science:

• Biomolecular design
• Protein engineering
• Supramolecular chemistry

Background:

• Proteins naturally form symmetrical assemblies, but designing such structures is challenging due to inherent protein asymmetry.
• Existing protein design methods struggle to create complex, symmetrical architectures with controlled assembly.

Purpose of the Study:

• To develop a novel method for designing symmetrical protein assemblies using inorganic chemistry.
• To create discrete, polyhedral protein cages with tightly packed shells and stimuli-responsive properties.

Main Methods:

• Utilized a 'one-pot' inorganic chemical approach coordinating soft (Fe3+) and hard (Zn2+) metal ions.
• Modified a monomeric protein (protomer) with hydroxamate groups and zinc-binding motifs.
• Achieved assembly into dodecameric and hexameric cages through concurrent metal ion coordination.

Main Results:

• Successfully assembled discrete dodecameric and hexameric protein cages resembling natural polyhedral architectures.
• Designed cages possess tightly packed shells without large apertures and exhibit stimuli-responsive assembly/disassembly.
• Achieved complex heterobimetallic stoichiometries, some of the most compositionally complex designed protein assemblies.

Conclusions:

• Demonstrated a versatile inorganic chemical strategy for de novo protein cage design.
• The developed method allows for precise control over protein assembly, symmetry, and responsiveness.
• These designed protein cages offer a new platform for biomolecular engineering and supramolecular chemistry applications.