Reversible Regulation of Protein Binding Affinity by a DNA Machine

Zhou, Chao; Yang, Zhongqiang; Li, Dongsheng

doi:10.1021/ja209590u

Cited by 122 publications

(101 citation statements)

References 35 publications

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“…1a. The design and construction of the nanotweezers, with B14-nm long arms, are based on a previous report 17 . A 25-nucleotide (nt) singlestranded DNA (ssDNA) oligomer (5 0 -TTTGCGTAAGACC CACAATCGCTTT-3 0 ) connects the ends of the tweezer arms and serves as a structural regulatory element to control the state of the tweezers (please see Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

“…DNA nanostructures are promising scaffolds for use in the organization of molecules on the nanoscale because they can be engineered to site-specifically incorporate functional elements in precise geometries [10][11][12] and to enable nanomechanical control capabilities 13,14 . Examples of such structures include autonomous walkers 15,16 , nanotweezers [17][18][19][20] and nanocages for controlled encapsulation and payload release 21,22 . New protein-DNA conjugation chemistries make it possible to precisely position proteins and other biomolecules on DNA scaffolds 23 , generating multi-enzyme pathways with the ability to modulate intermolecular interactions and the local environment [24][25][26][27][28][29][30] .…”

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confidence: 99%

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A DNA tweezer-actuated enzyme nanoreactor

et al. 2013

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The functions of regulatory enzymes are essential to modulating cellular pathways. Here, we report a tweezer-like DNA nanodevice to actuate the activity of an enzyme/cofactor pair. A dehydrogenase and NAD þ cofactor are attached to different arms of the DNA tweezer structure and actuation of enzymatic function is achieved by switching the tweezers between open and closed states. The enzyme/cofactor pair is spatially separated in the open state with inhibited enzyme function, whereas in the closed state, enzyme is activated by the close proximity of the two molecules. The conformational state of the DNA tweezer is controlled by the addition of specific oligonucleotides that serve as the thermodynamic driver (fuel) to trigger the change. Using this approach, several cycles of externally controlled enzyme inhibition and activation are successfully demonstrated. This principle of responsive enzyme nanodevices may be used to regulate other types of enzymes and to introduce feedback or feed-forward control loops.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

A DNA tweezer-actuated enzyme nanoreactor

et al. 2013

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“…By taking advantage of the high versatility and designability of DNA chemistry [9][10][11][12][13][14][15][16][17][18][19] several groups have recently developed pH-triggered DNA-based probes or nanomachines [20][21][22][23][24][25][26][27][28][29][30] . Such probes typically exploit DNA secondary structures that display pH-dependence due to the presence of specific protonation sites.…”

Section: Introductionmentioning

confidence: 99%

Programmable pH-Triggered DNA Nanoswitches

2014

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ABSTRACT:Here we have rationally designed a tunable DNA-based nanoswitch whose closing/opening can be triggered over specific different pH windows. This nanoswitch forms an intramolecular triplex DNA structure through pH-sensitive parallel Hoogsteen interactions. We demonstrate that by simply changing the relative content of TAT/CGC triplets in the switch we can rationally tune its pH-dependence over more than 5 pH units. By using a combination of such nanowitches with different pH sensitivity, we also demonstrate how we can engineer a pH nanosensor that can precisely monitor pH variations over 5.5 units of pH. With their fast response time (<200 msec) and high reversibility, these pH-triggered nanoswitches appear particularly suitable for applications ranging from the real-time monitoring of pH changes in-vivo to the development of pH sensitive smart nanomaterial.Nature often employs finely pH-regulated biomolecules to modulate and tune a number of biological activities 1 ranging from enzyme catalysis 2 to protein folding 3 , membrane function 4 and apoptosis 5 . For these reasons, developing probes, switches or nanomaterials that are able to respond to specific pH changes should prove of utility for several applications in the fields of in-vivo imaging, clinical diagnostics, and drug-delivery [6][7][8] .By taking advantage of the high versatility and designability of DNA chemistry 9-19 several groups have recently developed pH-triggered DNA-based probes or nanomachines [20][21][22][23][24][25][26][27][28][29][30] . Such probes typically exploit DNA secondary structures that display pH-dependence due to the presence of specific protonation sites. These structures include I-motif [21][22][23]26,29,31 , intermolecular triplex DNA 25,28,32 , DNA tweezers 20 and, more recently, the Amotif 33 . Despite the promising and advantageous characteristics of some of these DNA-based nanomachines, which include fast response times and sustained efficiency over several cycles, a drawback inevitably affects their performances: they all respond (with an exception 33a ) over a fixed pH window that typically spans 1.5 to 2 pH units 26,34,33b . These nanomachines, therefore, cannot be adapted to provide a useful output outside these fixed pH-windows.Here we describe a method to rationally design and program pH-triggered DNA-based nanoswitches whose pH-dependence can be finely tuned and modulated over more than 5 units of pH. We created our switches by taking advantage of the wellcharacterized pH sensitivity of the parallel Hoogsteen (T,C)-motif in triplex DNA [34][35][36] . To do so we have designed a DNAbased triplex pH-triggered nanoswitch that consists in a double intramolecular hairpin stabilized with both Watson-Crick (W-C) and parallel Hoogsteen interactions (Fig. 1). More specifically, one hairpin of the triplex nanoswitch is formed by the W-C hybridization of two 10-base complementary portions separated by a 5 base loop. This duplex DNA is then able to form a triplex structure via the formation of a second hairpin through...

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“…For example, Figure 4a shows two double-crossover motifs joined with a Holliday junction forming a tweezer-like DNA machine that can be opened (in the stem-loop orientation) and closed (in the double helix orientation) by the Spatial regulation of synthetic and biological nanoparticles Z Yang et al addition of the fuel and antifuel strand, respectively. 70 Two ligands can bind the target protein, thrombin, and are introduced at both terminals of the DNA tweezers. In the closed state, the two ligands are in a cooperative position and catch the thrombin.…”

Section: Dynamic Regulation Of Nps With Dnamentioning

confidence: 99%

Spatial regulation of synthetic and biological nanoparticles by DNA nanotechnology

Yang

Liu

2015

NPG Asia Mater

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Nanoparticles are among the most fascinating materials because of their unique size-dependent properties. The spatial positioning of the nanoparticles with a nanoscale precision will greatly enhance their potential for use in the fabrication of functional materials and devices. Recently, the development of DNA nanotechnology has enabled the construction of two-and three-dimensional, precisely addressable nanostructures and devices based on DNA sequence design and programmable assembly. Advances in conjugating DNA with nanoparticles can bridge these two technologies and provide scientists with a new tool to study material transportation and energy transfer at a nanometer scale. In this review, we summarize the recent progress in this emerging research field, which includes not only the static arrangements of inorganic nanoparticles but also the dynamic regulation of organic and biological units at a nanometer scale. With the rapid development in this field, new challenges and new possibilities will emerge and bring about fruitful achievements with a significant impact on future work.

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Reversible Regulation of Protein Binding Affinity by a DNA Machine

Cited by 122 publications

References 35 publications

A DNA tweezer-actuated enzyme nanoreactor

A DNA tweezer-actuated enzyme nanoreactor

Programmable pH-Triggered DNA Nanoswitches

Spatial regulation of synthetic and biological nanoparticles by DNA nanotechnology

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