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Constructing different protein nanostructures with high-order discrete architectures by using one single building block remains a challenge. Here, we present a simple, effective disulfide-mediated approach to prepare a set of protein nanocages with different geometries from single building block. By genetically deleting an inherent intra-subunit disulfide bond, we can render the conversion of an 8-mer bowl-like protein architecture (NF-8) into a 24-mer ferritin-like nanocage in solution, while selective insertion of an inter-subunit disulfide bond into NF-8 triggers its conversion into a 16-mer lenticular nanocage. Deletion of the same intra-subunit disulfide bond and insertion of the inter-subunit disulfide bond results in the conversion of NF-8 into a 48-mer protein nanocage in solution. Thus, in the laboratory, simple mutation of one protein building block can generate three different protein nanocages in a manner that is highly reminiscent of natural pentamer building block originating from viral capsids that self-assemble into protein assemblies with different symmetries.

Disulfide-mediated conversion of 8-mer bowl-like protein architecture into three different nanocages