Charged molecular glue discovery enabled by targeted degron display - Nature Chemical Biology The study reveals a ‘chemocentric’ strategy for identifying charged molecular glue degraders, through discovering a bromodomain-binding molecular glue degrader prodrug that is metabolically activated ...

Charged molecular glue discovery enabled by targeted degron display

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Munc13-4–STX7 inhibitors impair endosomal TLR activation and systemic inflammation - Nature Chemical Biology Endosomal Toll-like receptors (TLRs) are central to the innate immune response but their overactivation can cause systemic inflammation and disease. Now, new small molecules targeting the interaction ...

Inhibitors of Munc13-4-syntaxin 7, essential for endosomal maturation, impair endosomal TLR overactivation and systemic inflammation

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Dual cytosine modification through hydroxylation and arabinofuranosylation in phages - Nature Chemical Biology He et al. identified a cytosine hypermodification pathway in phage HY126. This pathway involves prereplicative deoxycytidine monophosphate hydroxylation and arabinofuranosylation, followed by postrepl...

A new paper reports a cytosine hypermodification pathway in phage HY126 that confers nuclease resistance

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Biomolecular condensates mediate C–N bond formation - Nature Chemical Biology Song et al. find that biomolecular condensates can catalyze reductive amination of metabolites through a nonenzymatic mechanism, mediating C–N bond formation in vitro and impacting cellular metabolism...

A new paper finds that biomolecular condensates can catalyze reductive amination of metabolites through a nonenzymatic mechanism, mediating C-N bond formation in vitro and impacting cellular metabolism in E. coli

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Trafficking of a nitrogenase FeMo-cofactor assembly intermediate - Nature Chemical Biology The maturation of the unique FeMo-cofactor of molybdenum nitrogenase is a multistep process requiring the sequential action of a series of maturase complexes. Here, the authors report on how cryo-elec...

The maturation of the unique FeMo-cofactor of molybdenum nitrogenase is a multistep process requiring the sequential action of a series of maturase complexes. Cryo-EM structures capture trafficking of a key intermediate of cofactor assembly

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The Focus issues features views from redox biologists on the next frontiers and most needed developments in the field

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Free to read link: rdcu.be/fbdwd

The cover image with negative-stain electron microscopy grid and structure highlights the diversity of heteromeric structures of peroxiredoxin involved in redox biology

Our April issue is live with a focus on redox chemical biology

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The cover image with negative-stain electron microscopy grid and structure highlights the diversity of heteromeric structures of peroxiredoxin involved in redox biology

FYI, the first transparent peer review file @natchembio.nature.com has been published with this paper 👀 Yes, we publish them now if the authors elect to!

A family portrait of lanmodulin selectivity for enhanced rare-earth separations - Nature Chemical Biology Proteins are promising ligands for selective metal capture, but low-throughput assays limit their discovery and design. Now, a high-throughput platform for quantifying the rare earth selectivity of la...

A new paper reports a high-throughput platform for quantifying the rare earth metal selectivity of lanmodulin proteins, enabling high-purity rare earth metal recovery and separations

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Activation and regulation of the dynein–dynactin–NuMA complex - Nature Chemical Biology NuMA activates dynein to organize the mitotic spindle by linking motor-driven transport with microtubule (MT) minus-end control. Mitotic phosphorylation relieves NuMA autoinhibition, enabling dynein m...

Activation and regulation of the dynein-dynactin-NuMa complex in organizing microtubules in mitotic spindle assembly

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IDO1 regulating ROS rhythm reveals glycogenolysis/PPP as a cancer treatment target - Nature Chemical Biology Increased reactive oxygen species (ROS) results in indoleamie-2,3-dioxygenase export to the cytosol, which converts tryptophan to kynurenine that binds glucose-6-phosphate dehydrogenase to enable NADP...

A new paper reports that IDO1 regulates rhythmic oscillations of ROS dynamics, which are lost in hypoxic tumor cells. AhR mediates disordered ROS accumulation, and dual inhibition of IDO1 and AhR is shown to be a potential cancer therapeutic strategy

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A new Comment discusses how an integrative cross-disciplinary research program in China aims to link RNA biology with traditional drug discovery to accelerate RNA innovation in RNA-centered therapeutics

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Iterative acylation on mature lasso peptides by widespread acetyltransferases - Nature Chemical Biology Traditional iterative catalysis in RiPP biosynthesis typically modifies linear peptides. Here the authors discover GNAT enzymes that iteratively modify fully folded lasso peptides and engineer them to...

Traditional iterative catalysis in RiPP biosynthesis typically modifies linear peptides. Here, the authors discover GNAT enzymes that iteratively modify fully folded lasso peptides and engineer them to create lipolasso peptides with expanded chemical diversity

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A druggable redox switch on SHP1 controls macrophage inflammation - Nature Chemical Biology Post-translational redox modification of protein cysteine residues has emerged as a mode of immune cell regulation. Now, a deep redox proteomics study identifies redox-regulated and druggable cysteine...

A deep redox proteomics study identifies redox-regulated and druggable cysteines in immune proteins

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Genetic recording and in situ readout of single-cell signaling memory - Nature Chemical Biology Hao et al. developed a CRISPR-based system that records cell signaling activity as DNA edits readable by imaging, enabling single-cell reconstruction of signal strength and revealing long-lasting memo...

A CRISPR-based system records cell signaling activity as DNA edits readable by imaging

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Chimerization expands peroxiredoxin scope - Nature Chemical Biology Although long considered to be structured as oligomers comprising a single species, recent work highlights the ability of eukaryotic type 1 peroxiredoxin isoforms to assemble as heterodimers and heter...

Chimerization expands peroxiredoxin scope – Check out the associated News & Views by Hortense Mazon, Benjamin Selles, and Sophie Rahuel-Clermont

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Hetero-oligomerization drives structural plasticity of eukaryotic peroxiredoxins - Nature Chemical Biology Peroxiredoxins from diverse organisms were found to assemble into hybrid complexes, not just identical ones. These mixed assemblies reshape structure and stability, challenging a long-held view of per...

Peroxiredoxins from diverse organisms are found to assemble into hybrid complexes, not just identical ones. These mixed assemblies reshape structure and stability, challenging a long-held view of peroxiredoxin assembly in cells

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Structures of ALG3/9/12 reveal the assembly logic of the N-glycan oligomannose core - Nature Chemical Biology Three endoplasmic reticulum luminal mannosyltransferases ALG3, ALG9 and ALG12 catalyze the synthesis of the branched mannose core in N-glycans in four distinct steps. Now, cryo-electron microscopy str...

The three enzymes ALG3, ALG9, and ALG12 catalyze the synthesis of the branched mannose core in N-glycans in four distinct steps. Now, their structures reveal the molecular logic of oligomannose core assembly #glycotime

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The Front Half includes Research Highlights on natural product discovery, GPCR signaling, and protein design and a Review on degron and degradation signals promoting substrate-E3 ligase interactions

The cover depicts the neuron as a plant with the nodules surrounding the roots representing condensates of SARM1, which lead to axonal fragmentation, illustrated as fractured roots. SARM1 contains a TIR domain, also found in plants, known to form condensates that trigger NADase activity.

Our March issue is live!

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The cover depicts the neuron as a plant with the nodules surrounding the roots representing condensates of SARM1, which lead to axonal fragmentation, illustrated as fractured roots

Excited to share our new Perspective in @natchembio.nature.com with @Yang_J_lab.

How do we move from isolated cysteine modifications to a systems-level understanding of redox signaling? We outline a unified chemical framework for decoding the cysteine redoxome.

Read here: t.co/6XY1FCdtN6

Mast cell extracellular granules are bioactive condensates assembled by heparin and polyamine - Nature Chemical Biology Mast cells are immune cells that release membraneless mast cell extracellular granules (MCEGs) in response to allergic inflammation and pathogen infection. MCEGs are found to be condensates formed thr...

Mast cell extracellular granules are found to be condensates formed through sugar-metabolite interactions with elevated pH and higher metal concentration that enrich and enhance the activity of immune modulators, such as cytokines and proteases

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Multifaceted roles for persulfide species in redox chemical biology - Nature Chemical Biology This Review discusses current research and future directions in protein persulfidation and polysulfidation to enable their full potential in redox-based therapeutic efforts.

A new Review discusses current research and future directions in protein persulfidation and polysulfidation to enable their full potential in redox-based therapeutic efforts

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Designing chemigenetic DNA nanotrap for norepinephrine dynamic imaging in organelles - Nature Chemical Biology Chen et al. developed a chemigenetic DNA nanoprobe enabling rapid and selective mapping of norepinephrine dynamics in organelles and discovered that norepinephrine bursts in the endoplasmic reticulum ...

A chemigenetic DNA nanoprobe enables rapid and selective mapping of norepinephrine dynamics in organelles and is used to show that norepinephrine bursts in the ER trigger neuronal death during traumatic brain injury

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Drug-controlled CAR T cells through the regulation of cell–cell interactions - Nature Chemical Biology Drug-controlled DROP-CARs enable reversible extracellular control of CAR T cell function via human-derived protein switches that modulate cell–cell interactions and support dual-antigen targeting as w...

Drug-controlled DROP-CARs enable reversible extracellular control of CAR T cell function via human-derived protein switches that modulate cell-cell interactions and support dual-antigen targeting as well as logic-gated signaling

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A two-step clockwork mechanism opens a proteo-lipidic pore in PIEZO2 - Nature Chemical Biology Mechanosensitive PIEZO channels sense and open through membrane tension, but their dynamic gating mechanisms at the molecular level remain unclear. A hybrid all-atom and coarse-grained molecular dynam...

Mechanosensitive PIEZO channels sense and open through membrane tension, but their dynamic gating mechanisms remain unclear. A multi-scale simulation approach and electrophysiology reveal a clockwork mechanism for PIEZO2 involving two open states

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High-throughput ligand diversification to discover chemical inducers of proximity - Nature Chemical Biology Molecular glue degraders have consistently been discovered retrospectively, despite their increasing importance. Herein, a high-throughput approach is described that modifies existing ligands into mol...

A high-throughput approach modifies existing ligands into molecular glue degraders

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Adhesion GPCR-induced ectocytosis mediates intercellular GPCR signal propagation - Nature Chemical Biology This study reveals that adhesion G-protein-coupled receptors (GPCRs) promote extracellular vesicle (EV) formation and EVs spread GPCRs into neighboring cells to activate G-protein signaling, providing...

A new paper reveals that adhesion GPCRs promote extracellular vesicle (EV) formation and EVs spread GPCRs into neighboring cells to activate G-protein signaling, providing a novel mechanism for cell-cell communication

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NCBP1 stress signaling drives alternative S6K1 splicing inhibiting translation - Nature Chemical Biology Chang et al. found that nuclear reactive electrophile stress suppresses translation through HNEylation at C436 of NCBP1, triggering alternative splicing of S6K1, a key regulator of translation.

Nuclear reactive electrophilic stress suppresses translation through HNEylation at C436 of NCBP1, triggering alternative splicing of S6K1, a key regulator of translation

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A pharmacological modality to sequester homomeric proteins - Nature Chemical Biology Polymerization-inducing chimeras are a novel bifunctional modality that uses protein symmetry to sequester targets by forming insoluble supramolecular assemblies. This approach overcomes reliance on a...

Polymerization-inducing chimeras (PINCHs) are a novel bifunctional modality that sequesters target homodimers in a polymeric state, thereby inhibiting their function

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