Programming conformational cooperativity to regulate allosteric protein-oligonucleotide signal transduction

Liu, Yuan; Qie, Yunkai; Yang, Jing; Wu, Ranfeng; Cui, Shuang; Zhao, Yuliang; Anderson, Gregory J.; Nie, Guangjun; Li, Suping; Zhang, Cheng

doi:10.1038/s41467-023-40589-z

Cited by 9 publications

(1 citation statement)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Currently, [ 22,34 ] signal transduction techniques have garnered considerable interest because of their evolution across a wide range of molecular pathways and signaling networks. [ 35 ] In contrast to the reported cooperative strategy that focuses on programming multiple conformational signals exclusively to regulate protein‐oligonucleotide signal transduction, our design involves two another transduction PST switches based on DNA aptamers for non‐nucleic acid molecules (Figure 3A): tumor progression‐associated adenosine‐5′‐triphosphate (ATP) and arterial thrombosis‐related thrombin (THR) are representative markers of the most studied small molecules and proteins, respectively. When a target molecule binds to the DNT, the proximity effect created by the irregular folding of the target binding sites results in SDR.…”

Section: Resultsmentioning

confidence: 99%

A Spatially Controlled Proximity Split Tweezer Switch for Enhanced DNA Circuit Construction and Multifunctional Transduction

Bai,

Zhang,

Zhang

et al. 2023

Small

View full text Add to dashboard Cite

DNA strand displacement reactions are vital for constructing intricate nucleic acid circuits, owing to their programmability and predictability. However, the scarcity of effective methods for eliminating circuit leakages has hampered the construction of circuits with increased complexity. Herein, a versatile strategy is developed that relies on a spatially controlled proximity split tweezer (PST) switch to transduce the biomolecular signals into the independent oligonucleotides. Leveraging the double‐stranded rigidity of the tweezer works synergistically with the hindering effect of the hairpin lock, effectively minimizing circuit leakage compared with sequence‐level methods. In addition, the freely designed output strand is independent of the target binding sequence, allowing the PST switch conformation to be modulated by nucleic acids, small molecules, and proteins, exhibiting remarkable adaptability to a wide range of targets. Using this platform, established logical operations between different types of targets for multifunctional transduction are successfully established. Most importantly, the platform can be directly coupled with DNA catalytic circuits to further enhance transduction performance. The uniqueness of this platform lies in its design straightforwardness, flexibility, scalable intricacy, and system compatibility. These attributes pave a broad path toward nucleic acid‐based development of sophisticated transduction networks, making them widely applied in basic science research and biomedical applications.

show abstract

Section: Resultsmentioning

confidence: 99%

A Spatially Controlled Proximity Split Tweezer Switch for Enhanced DNA Circuit Construction and Multifunctional Transduction

Bai,

Zhang,

Zhang

et al. 2023

Small

View full text Add to dashboard Cite

show abstract

Aptamer‐Based DNA Allosteric Switch for Regulation of Protein Activity

Sun,

Zhao,

et al. 2024

Advanced Science

View full text Add to dashboard Cite

Allostery is a fundamental way to regulate the function of biomolecules playing crucial roles in cell metabolism and proliferation and is deemed the second secret of life. Given the limited understanding of the structure of natural allosteric molecules, the development of artificial allosteric molecules brings a huge opportunity to transform the allosteric mechanism into practical applications. In this study, the concept of bionics is introduced into the design of artificial allosteric molecules and an allosteric DNA switch with an activity site and an allosteric site based on two aptamers for selective inhibition of thrombin activity. Compared with the single aptamer, the allosteric switch possesses a significantly enhanced inhibition ability, which can be precisely regulated by converting the switch states. Moreover, the dynamic allosteric switch is further subjected to the control of the DNA threshold circuit for realizing automatic concentration determination and activity inhibition of thrombin. These compelling results confirm that this allosteric switch equipped with self‐sensing and information‐processing modules puts a new slant on the research of allosteric mechanisms and further application of allosteric tactics in chemical and biomedical fields.

show abstract

Engineering Modular DNA Reaction Networks for Signal Processing

Cui,

Liu,

Zhang

et al. 2024

Chemistry A European J

Self Cite

View full text Add to dashboard Cite

Diversified molecular information‐processing methods have significant implications for nanoscale manipulation and control, monitoring and disease diagnosis of organisms, and direct intervention in biological activities. However, as an effective approach for implementing multifunctional molecular information processing, DNA reaction networks (DRNs) with numerous functionally specialized molecular structures have challenged them on scale and modular design, leading to increased network complexity, further causing problems such as signal leakage, attenuation, and cross‐talk in network reactions. Our study developed a strategy for performing various signal‐processing tasks through engineering modular DRNs composed of simple molecular structures. This strategy is based on a universal core unit with signal selection capability, and a timeadjustable signal self‐resetting module is achieved by combing the core unit and self‐resetting unit, which improves the time controllability of modular DRNs. In addition, multi‐input and ‐output signal crosscatalytic and continuously adjustable signal delay modules were realized by combining core and threshold units, providing a flexible, precise method for modular DRNs to process the signal. The strategy simplifies the design of DRNs, helps generate design ideas for largescale integrated DRNs with multiple functions, and provides prospects in biocomputing, gene regulation, and biosensing.

show abstract

Programming conformational cooperativity to regulate allosteric protein-oligonucleotide signal transduction

Cited by 9 publications

References 65 publications

A Spatially Controlled Proximity Split Tweezer Switch for Enhanced DNA Circuit Construction and Multifunctional Transduction

A Spatially Controlled Proximity Split Tweezer Switch for Enhanced DNA Circuit Construction and Multifunctional Transduction

Aptamer‐Based DNA Allosteric Switch for Regulation of Protein Activity

Engineering Modular DNA Reaction Networks for Signal Processing

Contact Info

Product

Resources

About