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

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.