Protein‐Controlled Actuation of Dynamic Nucleic Acid Networks by Using Synthetic DNA Translators**

Abstract

Integrating dynamic DNAn anotechnology with protein-controlled actuation will expand our ability to process molecular information. We have developed as trategy to actuate strand displacement reactions using DNA-binding proteins by engineering synthetic DNAtranslators that convert specific protein-binding events into trigger inputs through ap rogrammed conformational change.W eh ave constructed synthetic DNAn etworks responsive to two different DNAbinding proteins,T ATA-binding protein and Myc-Max, and demonstrated multi-input activation of strand displacement reactions.W ea chieved protein-controlled regulation of as ynthetic RNAa nd of an enzyme through artificial DNA-based communication, showing the potential of our molecular system in performing further programmable tasks.

Protein–Protein Communication Mediated by an Antibody‐Responsive DNA Nanodevice**

“…A widely used approach to this end is the rational design of synthetic DNA/protein communication that takes advantage of the many naturally occurring proteins that recognize and bind specific oligonucleotide sequences to, for example, regulate transcription or translation [15–21] . Such sequence‐specific recognition has been employed in synthetic systems to regulate the load/release of molecular cargos from DNA‐based devices, [22] the assembly/disassembly of DNA‐based structures [23] and DNA‐based reactions [24] …”

Biosupramolecular Systems: Integrating Cues into Responses

“…The wealth of geometric based inputs exploited in biosupramolecular networks are not limited to simply changing the broad positional proximity of the components, but can also modify the relative internal proximity of systems through conformational changes. Such systems can include the interaction between DNA-binding proteins (TATA, Myc-Max) with metastable nucleic acid hairpins to induce a conformational change 91 or de novo orthogonal key-latch proteins which can be recruited by cell surface receptors such as HER2, EGFR, and EpCAM. 92 Coupling of a geometric change between an enzyme and its inhibitor to hybridization has also been used as an on/off input to control enzymatic activity 40,41,56,93,94 and reconstitute split proteins.…”

“…Owing to the proximity dependence of the FRET process, this readout is often coupled to processes which result in changes in geometry or localization, including the association or dissociation of binding partners (be these protein or nucleic acid based) bearing the FRET pairs, cleavage events (such as by nucleases or proteases), and intramolecular (or pseudo intramolecular) conformational changes which modify the relative positioning of the FRET pairs in space. The most common FRET pair used in biosupramolecular networks comprises the cyanine dyes Cy3/Cy5, ,,,,, while so-called quenchers such as dabsyl, ,,,, black hole quenchers (BHQ), QSY21, and Iowa Black , have also found wide utility for FRET-based turn on/off systems. Additionally, FRET protein pairs such as cyan fluorescent protein (CFP) and yellow fluorescent protein (YFP) have also found utility as outputs in biosupramolecular networks .…”

A kinetically controlled platform for ligand-oligonucleotide transduction

“…For instance, riboswitch, a typical example that has been widely discovered in cells, is a class of regulatory RNA aptamers in which ligand-induced strand displacement of nucleic acids can regulate specific gene expressions 29 , 56 , 57 . Not limited to aptamers, some other types of ligand-nucleic acid interactions can also function through the competition behavior to regulate the strand dynamics 58 . Overall, taking this strategy of transducing the ligands into strand-displacement reactions, plenty of biosensors and biomaterials, as well as the gene-regulating applications of synthetic riboswitches, have been greatly developed.…”