Programming conformational cooperativity to regulate allosteric protein-oligonucleotide signal transduction

Article Biotechnology & Applied Microbiology

Improving cooperativity of transcription activators by oligomerization domains in mammalian cells

Xinmao Chen et al.

Summary: In this study, a cooperative transcription factor was developed by fusing oligomerization domain in mammalian cells, which is critical for the applications of synthetic biology in mammalian cells.

SYNTHETIC AND SYSTEMS BIOTECHNOLOGY (2023)

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Review Biochemistry & Molecular Biology

Nucleic acid drug vectors for diagnosis and treatment of brain diseases

Zhi-Guo Lu et al.

Summary: Nucleic acid drugs have advantages in brain disease treatment, but their effectiveness is influenced by physiological barriers and individual differences. This review provides a classification of nucleic acid drugs, discusses physiological barriers and coping strategies during drug delivery, and explores multidrug regimens and corresponding vectors for brain disease treatment. It also addresses the feasibility of patient stratification and personalized therapy through diagnostic information from medical imaging and the introduction of contrast agents into vectors. The future feasibility and challenges of vector-based integrated diagnosis and gene therapy for brain diseases are also discussed.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2023)

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Article Chemistry, Multidisciplinary

Cooperativity as quantification and optimization paradigm for nuclear receptor modulators

Pim J. de Vink et al.

Summary: This study proposes a cooperativity mechanism for small molecule modulation of nuclear receptor-protein interactions. By using a thermodynamic model and three-body binding events, the reciprocal effects of nuclear receptor-coregulator binding and nuclear receptor-ligand binding are dissected and quantified. This provides a new conceptual way of thinking about structure-activity relationships for nuclear receptor ligands and has implications for the discovery and optimization of nuclear receptor modulators.

CHEMICAL SCIENCE (2022)

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Article Multidisciplinary Sciences

Programmable allosteric DNA regulations for molecular networks and nanomachines

Cheng Zhang et al.

Summary: A general and programmable strategy for allosteric DNA regulations was developed, allowing precise control through varying the dimensions, positions, and number of conformational signals. This strategy enables the creation of fan-out/fan-in DNA gates, multiple-layer DNA cascading networks, and long-range allosteric signal transmission. It has significant implications for nano-engineering, chemical, and biomedical applications.

SCIENCE ADVANCES (2022)

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Article Multidisciplinary Sciences

Signal transduction in light-oxygen-voltage receptors lacking the active-site glutamine

Julia Dietler et al.

Summary: This study investigates whether light-oxygen-voltage (LOV) photoreceptors can transduce light signals in the absence of a conserved glutamine residue. Results show that LOV photoreceptors can still generate effective signaling responses even without this key glutamine. Further structural analysis reveals highly similar light-induced conformational changes regardless of the presence of the glutamine. These findings have implications for biotechnological applications and suggest the evolutionary descent of LOV photoreceptors from redox-active flavoproteins.

NATURE COMMUNICATIONS (2022)

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Article Multidisciplinary Sciences

ATP-competitive inhibitors modulate the substrate binding cooperativity of a kinase by altering its conformational entropy

Cristina Olivieri et al.

Summary: ATP-competitive inhibitors are a major class of drugs for protein kinases. Using protein kinase A as a model system, this study shows that different ATP-competitive inhibitors modulate substrate binding cooperativity by tuning the conformational entropy of the kinase. The findings propose a new paradigm for the discovery of ATP-competitive inhibitors based on their ability to modulate the allosteric coupling between nucleotide and substrate-binding sites.

SCIENCE ADVANCES (2022)

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Article Biochemistry & Molecular Biology

A PKA inhibitor motif within SMOOTHENED controls Hedgehog signal transduction

John T. Happ et al.

Summary: This study reveals that SMO uses a pseudosubstrate sequence to block the active site of PKA, extinguishing its enzymatic activity and releasing GLI for signal transduction. The interference with SMO-PKA interactions prevents Hh signal transduction.

NATURE STRUCTURAL & MOLECULAR BIOLOGY (2022)

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Article Chemistry, Multidisciplinary

Branched Antisense and siRNA Co-Assembled Nanoplatform for Combined Gene Silencing and Tumor Therapy

Jianbing Liu et al.

Summary: This study presents a novel strategy for constructing a nanoplatform that combines branched antisense DNA and siRNA for gene silencing. The multifunctional nucleic acid nanosystem efficiently inhibits tumor growth by targeting the tumor-associated gene PLK1 through combined gene silencing.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2021)

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Article Biochemistry & Molecular Biology

Trivalent PROTACs enhance protein degradation via combined avidity and cooperativity

Satomi Imaide et al.

Summary: Tri-valent PROTACs with increased binding valency enhance protein degradation efficacy and anti-cancer activity, forming highly stable ternary complexes with positive cooperativity. SIM1 engages with both BET bromodomains with high avidity and forms a productive 1:1:1 complex with VHL, demonstrating prolonged residence time and improved functional outcomes.

NATURE CHEMICAL BIOLOGY (2021)

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Article Multidisciplinary Sciences

Sulfated polysaccharide directs therapeutic angiogenesis via endogenous VEGF secretion of macrophages

Yuanman Yu et al.

Summary: A study found that semisynthetic sulfated chitosan (SCS) can induce angiogenesis by increasing the secretion of VEGF by macrophages, aiding in the treatment of ischemic diseases. SCS works through the VEGF-VEGFR2 signaling pathway, and inhibiting VEGF or VEGFR2 signals can affect the role of macrophages in angiogenesis.

SCIENCE ADVANCES (2021)

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Article Chemistry, Multidisciplinary

A biologically stable DNAzyme that efficiently silences gene expression in cells

Yajun Wang et al.

Summary: Efforts to use RNA-cleaving DNA enzymes as gene-silencing agents have been hindered by low efficacy in clinical trials, but a new xeno-nucleic-acid-modified DNAzyme called X10-23 has shown promise in achieving multiple-turnover activity and resisting nuclease digestion in cellular conditions. X10-23 overcomes product inhibition and facilitates persistent gene silencing in mammalian cells, suggesting new molecular chemotypes can enhance the activity and stability of DNAzymes for potential therapeutic applications.

NATURE CHEMISTRY (2021)

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Review Pharmacology & Pharmacy

Nucleic acid delivery for therapeutic applications

Akash Gupta et al.

Summary: This review discusses various therapeutic applications of nucleic acids targeted at specific diseases and tissues, highlighting recent technologies that have advanced to late-stage clinical trials and received FDA approval.

ADVANCED DRUG DELIVERY REVIEWS (2021)

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Article Biotechnology & Applied Microbiology

Noncoding RNA therapeutics - challenges and potential solutions

Melanie Winkle et al.

Summary: In recent years, RNA-based therapies have gained FDA approval, but there are still challenges in targeting ncRNAs. Therapeutic targeting of noncoding RNAs has the potential to become a new approach for treating diseases such as cancer.

NATURE REVIEWS DRUG DISCOVERY (2021)

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Article Multidisciplinary Sciences

A kinetically controlled platform for ligand-oligonucleotide transduction

Qiu-Long Zhang et al.

Summary: Ligand-oligonucleotide interactions provide a critical pathway to integrate non-nucleic acid molecules into nucleic acid circuits, with ligand-aptamer complexes designed to control strand-displacement reactions for versatile transduction. This platform offers unique features such as design simplicity, expandable complexity, and system compatibility that may lead to the development of sophisticated nucleic acid-based transduction networks.

NATURE COMMUNICATIONS (2021)

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Article Multidisciplinary Sciences

Pseudoknot length modulates the folding, conformational dynamics, and robustness of Xrn1 resistance of flaviviral xrRNAs

Xiaolin Niu et al.

Summary: The study reveals that the length of long-range pseudoknot in flaviviral xrRNA modulates the Mg2+-dependence and significantly impacts its folding, conformational dynamics, and Xrn1 resistance.

NATURE COMMUNICATIONS (2021)

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Article Chemistry, Multidisciplinary

Programming folding cooperativity of the dimeric i-motif with DNA frameworks for sensing small pH variations

Shiliang He et al.

Summary: The response sensitivity of a molecular sensor depends on the folding cooperativity of its responsive module. This can be enhanced through preorganization, as demonstrated with an H+-responsive dimeric DNA i-motif, to create robust intracellular pH sensors with high response sensitivity.

CHEMICAL COMMUNICATIONS (2021)

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Correction Multidisciplinary Sciences

Orthogonal regulation of DNA nanostructure self-assembly and disassembly using antibodies (vol 10, 5509, 2019)

Simona Ranallo et al.

NATURE COMMUNICATIONS (2020)

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Structural basis for allosteric PARP-1 retention on DNA breaks

Levani Zandarashvili et al.

SCIENCE (2020)

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Modular protein-oligonucleotide signal exchange

Deepak K. Agrawal et al.

NUCLEIC ACIDS RESEARCH (2020)

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

Alessandro Bertucci et al.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2020)

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Aptamers in RNA-based switches of gene expression

Maike Spoering et al.

CURRENT OPINION IN BIOTECHNOLOGY (2020)

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Phosphoregulated orthogonal signal transduction in mammalian cells

Leo Scheller et al.

NATURE COMMUNICATIONS (2020)

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Using antibodies to control DNA-templated chemical reactions

Lorena Baranda Pellejero et al.

NATURE COMMUNICATIONS (2020)

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Article Biochemical Research Methods

Aptamer-Mediated Control of Polyadenylation for Gene Expression Regulation in Mammalian Cells

Maike Spoering et al.

ACS SYNTHETIC BIOLOGY (2020)

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Review Medicine, Research & Experimental

Therapeutic Antisense Oligonucleotides Are Coming of Age

C. Frank Bennett

ANNUAL REVIEW OF MEDICINE, VOL 70 (2019)

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Globally correlated conformational entropy underlies positive and negative cooperativity in a kinase's enzymatic cycle

Yingjie Wang et al.

NATURE COMMUNICATIONS (2019)

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Complex signal processing in synthetic gene circuits using cooperative regulatory assemblies

Caleb J. Bashor et al.

SCIENCE (2019)

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A binding cooperativity switch driven by synergistic structural swelling of an osmo-regulatory protein pair

Abhishek Narayan et al.

NATURE COMMUNICATIONS (2019)

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Kinome-Wide Screening with Small Interfering RNA Identified Polo-like Kinase 1 as a Key Regulator of Proliferation in Oral Cancer Cells

Yih-Gang Goan et al.

CANCERS (2019)

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An Allosteric Switch Primes Sequence-Specific DNA Recognition

Matthew J. Walker et al.

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Antisense oligonucleotides: the next frontier for treatment of neurological disorders

Carlo Rinaldi et al.

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Natural inspirations for metal-ligand cooperative catalysis

Matthew D. Wodrich et al.

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Programmable Nucleic Acid Nanoswitches for the Rapid, Single-Step Detection of Antibodies in Bodily Fluids

Alessandro Porchetta et al.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2018)

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Antibody-Bridged Beacon for Homogeneous Detection of Small Molecules

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Controlled membrane translocation provides a mechanism for signal transduction and amplification

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Nongenetic Reprogramming of the Ligand Specificity of Growth Factor Receptors by Bispecific DNA Aptamers

Ryosuke Ueki et al.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2017)

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Allosteric DNA nanoswitches for controlled release of a molecular cargo triggered by biological inputs

Marianna Rossetti et al.

CHEMICAL SCIENCE (2017)

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Allosteric pyruvate kinase-based logic gate synergistically senses energy and sugar levels in Mycobacterium tuberculosis

Wenhe Zhong et al.

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Antibody-controlled actuation of DNA-based molecular circuits

Wouter Engelen et al.

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Antibody-powered nucleic acid release using a DNA-based nanomachine

Simona Ranallo et al.

NATURE COMMUNICATIONS (2017)

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AKT/PKB Signaling: Navigating the Network

Brendan D. Manning et al.

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Backbone NMR reveals allosteric signal transduction networks in the β1-adrenergic receptor

Shin Isogai et al.

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An intrinsically disordered entropic switch determines allostery in Phd-Doc regulation

Abel Garcia-Pino et al.

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Conformational photoswitching of a synthetic peptide foldamer bound within a phospholipid bilayer

Matteo De Poli et al.

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Allosteric regulation in NMDA receptors revealed by the genetically encoded photo-cross-linkers

Meilin Tian et al.

SCIENTIFIC REPORTS (2016)

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A Modular, DNA-Based Beacon for Single-Step Fluorescence Detection of Antibodies and Other Proteins

Simona Ranallo et al.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2015)

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Cooperativity, allostery and synergism in ligand binding to riboswitches

Alla Peselis et al.

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Protein-Protein Communication and Enzyme Activation Mediated by a Synthetic Chemical Transducer

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Enzyme-Artificial Enzyme Interactions as a Means for Discriminating among Structurally Similar Isozymes

Karuthapandi Selvakumar et al.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2015)

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Allosteric transcriptional regulation via changes in the overall topology of the core promoter

Steven J. Philips et al.

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A dynamically coupled allosteric network underlies binding cooperativity in Src kinase

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Dynamic DNA Assemblies Mediated by Binding-Induced DNA Strand Displacement

Feng Li et al.

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End-to-end conformational communication through a synthetic purinergic receptor by ligand-induced helicity switching

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Probing Allostery Through DNA

Sangjin Kim et al.

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Rational Design of Allosteric Inhibitors and Activators Using the Population-Shift Model: In Vitro Validation and Application to an Artificial Biosensor

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Cooperativity and biological complexity

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Cooperativity in macromolecular assembly

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Ligand-induced conformational changes allosterically activate Toll-like receptor 9

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Programming conformational cooperativity to regulate allosteric protein-oligonucleotide signal transduction

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