Abstract
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.
Highlights
Constructing different protein nanostructures with high-order discrete architectures by using one single building block remains a challenge
These two subunits form a dimer with a ratio of 1:1, and four of them assemble into an 8-mer protein architecture with C4 symmetry[13]
We have described here a protein-engineering approach to convert the 8-mer protein assembly with C4 symmetry into the 16-mer, 24mer, and 48-mer protein nanocages with higher symmetry by controlling the intra- or inter-subunit disulfide bond
Summary
Constructing different protein nanostructures with high-order discrete architectures by using one single building block remains a challenge. The number and structure of naturally occurring proteins are limited, thereby impeding their further applications as biotemplates or vehicles in the field of nanoscience and nanotechnology To overcome this limitation, different methods, including the matching rotational symmetry approach[26,27], computational interface design[28,29], and directed evolution have been explored to create different protein cages[20], but these approaches are usually engineering-intensive for protein surface and highly dependent on the accuracy of the design, thereby negatively impacting the biological activity of the designed protein. We believe that cysteine (Cys)-mediated disulfide bonds fit this approach well because (1)
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