DNA-Templated Assembly of Protein Complexes at Nanoscale

Directed, biologically-driven self-assembly has the potential to yield hybrid multicomponent architectures with applications ranging from sensors and diagnostics to nanoelectronic devices. Critical to these applications is to gain control over the precise orientation and geometry of biomolecules interacting with one-another and with surfaces. Such control has thus far been difficult to achieve in even the simplest biomolecular designs. Using a novel strategy for generation of multicomponent biological nanoarchitectures, the DNA-templated assembly of multiprotein complexes recognizing methylated DNA was achieved. The reassembly of two fragments of TEM-1 βlactamase, each one fused with a specific DNA recognition factor, into a catalytically active protein was achieved by using the cognate DNA elements of these factors. This strategy could potentially become a useful tool in studies of genomic DNA methylation in the context of cellular epigenetic processes.