Shape‐Complementary DNA Scaffold for Programmable Functionalization of Symmetric Protein Assemblies

ABSTRACT

The precise programming of bond valency, interaction strength, and spatial positioning within protein assemblies represents a significant step toward addressable functionalization, affording refined control over pattern recognition, cooperative behavior, and structural self‐organization. Here, we introduce a generalizable strategy to regulate the valency of symmetric protein assemblies through a shape‐complementary DNA scaffold. We demonstrate the controlled transfer of streptavidin–DNA conjugates from a ring‐shaped DNA nanostructure to a recombinant tobacco mosaic virus (TMV) disk. This mechanism specifies the number, sequence identity, and spatial arrangement of DNA motifs along the disk periphery, thereby enabling site‐specific addressability for DNA‐mediated binding and functional labeling. Leveraging the intrinsic programmability of DNA nanostructures, this strategy establishes a versatile platform for high‐fidelity valency engineering across diverse protein modules, with potential applications in biomedical and bioengineering.