Allostery of DNA nanostructures controlled by enzymatic modifications

Abstract

Allostery is comprehensively studied for natural macromolecules, such as proteins and nucleic acids. Here, we present controllable allostery of synthetic DNA nanostructure–enzyme systems. Rational designs of the synthetic allosteric systems are based on an in-depth understanding of allosteric sites with several types of strand placements, whose varying stacking strengths determine the local conformation and ultimately lead to a gradient level of allosteric transition. When enzymes in a molecular cloning toolbox such as DNA polymerase, exonuclease and ligase are applied to treat the allosteric sites, the resulting local conformational changes propagate through the entire structure for a global allosteric transition.

Controllable dynamics of complex DNA nanostructures

“…4E). 48 Bellot and colleagues developed an enzyme-sensitive DNA origami ‘nanoactuator’ device, which can be activated by the restriction enzyme BamHI and can then drive the configuration to the open state (Fig. 4F).…”

“…47 (E) Allosteric transitions of DNA nanostructures upon different enzymatic processes. 48 (F) A restriction enzyme-sensitive DNA origami device. 49 (G) CRISPR-Cas12a-catalyzed reconfiguration of a DNA origami structure.…”

Dynamic Reconfigurable DNA Nanostructures, Networks and Materials

“…Furthermore, triggered single‐cycle reconfiguration of DNA assemblies to programmed engineered nanostructures was demonstrated [72] . For example, the biocatalytic reconfiguration of wireframe origami scaffolds into rigidified tubules, [72b] the allosteric polymerase‐induced gap filling of flexible origami frameworks, [72c] or the G‐quadruplex‐stimulated reconfiguration of origami domino arrays into rigidified structures [72d] were established. Indeed, functional DNA frameworks were used as platforms guiding dynamic processes, [73] such as robotic cargo‐sorting walkers or fuel‐driven catalytic systems [74] .…”

Steric Communication between Dynamic Components on DNA nanodevices

“…Other studies have leveraged the precise geometric design of DNA origami 33,34 to demonstrate larger motions in nanostructures exhibiting conformational changes involving stiff links coupled by flexible joints 7,8 to achieve kinematically constrained motion, or in devices where conformational changes propagate among small repetitive structural units 30,35 . Such deployable structures allow for the transfer of forces and motions among large DNA components, which have been used to control molecular interactions 31,36 , and can be combined with triggering events, such as local enzymatic modifications or binding of an input molecule, to regulate device properties at distal locations 36,37 . Introduction of such conformational changes enables for allosteric communication.…”