Programmable Protein-DNA Composite Nanostructures: from Nanostructure Construction to Protein-Induced Micro-Scale...

The integration of DNA and protein-designed nanostructures represents a transformative approach to the development of programmable biopolymers for nanoscale construction. While DNA nanostructures excel in the readily programmable precision and scalability of base pairing, protein assemblies exploit the chemical diversity of amino acids for greater functional versatility. Here a platform is presented that unifies these two paradigms by combining coiled-coil protein origami with DNA nanostructures through orthogonal protein-protein (SpyCatcher-SpyTag) and protein-DNA (DCV-DNA) covalent conjugation strategies. This dual-functionalization strategy enables the construction of stable and versatile protein-DNA composites capable of hierarchical self-assembly. This shows that these composites drive the transformation of DNA nanotubes into large-scale, patterned nanofibers or nanorods, with the proteins regularly distributed over their surface and retaining their enzymatic and fluorescent functions. In addition, a DNA-luciferase circuit is developed through split enzyme reconstitution to achieve reversible regulation of enzymatic activity, highlighting the dynamic functionality of these composites. This introduces a modular approach to producing multifunctional bio-nanomaterials, highlighting the potential of protein-DNA composite nanostructures as a bridge between molecular design and functional nanomaterials and paves the way for the development of dynamic bio-devices and programmable biomaterials.