title: Controlled hierarchical assembly of switchable DNA-multiprotein complexes.
abstract: Directed, biologically-driven self-assembly has the potential to yield hybrid multicomponent architectures with applications ranging from sensors and diagnostics to catalysts and responsive materials. To enable these applications, it is critical 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. We report a novel methodology for the design and synthesis of functional, oriented, and reversibly switchable hierarchical assemblies at the nanoscale using DNA-protein and protein-protein interactions. The biomolecular assembly relies on the highly selective recognition between transcription factors (TFs) and their cognate DNA motifs that serve as transcription factor binding sites (TFBSs) along with the calmodulin (CaM)-calmodulin binding peptide (CBP) interaction that is regulated by Ca2+. Through these two types of controllable interactions, we achieved the sequential and hierarchical self-assembly of multiprotein complexes complete with embedded fluorescence and catalytic capabilities, which may serve as a paradigm for multifunctional assemblies.
authors.affiliation: Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, New York 12180-3590, USA.
authors.forename: Grazyna E
authors.initials: GE
authors.lastname: Sroga
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Dordick
mesh_terms: D001710:Biotin / Q000378:metabolism; D019921:Biotinylation; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000737:chemistry; D004247:DNA / Q000378:metabolism* / Q000648:ultrastructure; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D004800:Enzymes, Immobilized; D004926:Escherichia coli / Q000235:genetics / Q000254:growth & development; D005798:Genes, Bacterial / Q000235:genetics; D005982:Glutathione Transferase / Q000378:metabolism; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D009154:Mutation; D010957:Plasmids; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000302:isolation & purification / Q000378:metabolism / Q000648:ultrastructure; D012486:Salmonella typhimurium / Q000235:genetics; D019809:Streptavidin / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D002147:Calmodulin; D004268:DNA-Binding Proteins; D004800:Enzymes, Immobilized; D046912:Multiprotein Complexes; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D001710:Biotin; D004247:DNA; D019809:Streptavidin; D005982:Glutathione Transferase; D002118:Calcium