Researchers Design Quasisymmetric Protein Cages Using Computational Methods

Researchers developed a computational design method to create two-component protein cages that assemble into quasisymmetric structures. The approach uses geometric frustration to produce trimeric and dimeric components that form hexagonal assemblies with curvature-inducing pentagonal defects.

The components co-assemble into closed sphere-like cages, as confirmed by electron microscopy. By varying the curvature encoded in the dimeric linkers, the team produced cages with diameters from 40 to over 200 nanometers and molecular weights from 2 MDa to over 50 MDa.

These dimensions are comparable to natural virus capsids. The cages were further modified with additional protein domains to support ribonucleoprotein cargo loading and cellular uptake.

Fluorescently labelled cage assemblies were expressed in mammalian cells. The assemblies functioned as rheological probes and cargo recruiters, allowing researchers to examine size-dependent cytoplasmic diffusion and protein localization. The study demonstrates that quasisymmetric architectures previously observed in viral capsids can now be generated through computational protein design.