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The cryo-EM structures of Cas12g in complex with sgRNA in the absence and presence of target RNA reveal that the duplex formed by target RNA and crRNA binds to a central channel of Cas12g, inducing its conformational change and activation.
In honey bee colonies infested with the mite Varroa destructor, six Varroa-parasitization-specific (VPS) compounds trigger protective behavior in the bees, which are able to distinguish VPS compounds from healthy signals and recognize an infested brood.
E3 ligase subunit protein Fbxo48 interacts with phosphorylated Ampkα and mediates its proteasomal degradation. Interruption of the pAmpkα/Fbxo48 interaction by a small-molecule BC1618 promoted Ampkα activation and improved insulin sensitivity.
Crystal structures of a cobalamin-dependent radical S-adenosylmethionine (SAM) methylase reveal an unexpected mechanism that involves substrate-assisted catalysis whereby the carboxylate group of the co-substrate SAM serves as a general base.
Structural analysis of the A2058-dimethylated and unmethylated 70S ribosome complex alone and in combination with macrolides reveals the role of the desosamine moiety of macrolides in drug binding and resistance.
Bacteriophage single-stranded DNA annealing proteins (SSAPs) interact with the C termini of single-stranded binding proteins in host bacteria, a finding that enables engineering of enhanced SSAP portability and DNA recombineering activities.
A chemical screen identified BET bromodomain inhibitors as promoters of keratinocyte regenerative function and skin wound healing. Specifically, low-dose transient treatment with BET inhibitors imposes an activated, migratory state in keratinocytes.
Unlike other amine oxidase-family enzymes, nicotine oxidoreductase (NicA2) reacts very slowly with oxygen, prompting the search for and identification of a cytochrome c protein (CycN) that is responsible for accepting electrons from NicA2 in vivo.
Laboratory evolution of the bacterial transpeptidase sortase A coupled with yeast display selection enables a change of the enzyme’s substrate preference to recognize and covalently label endogenous amyloid-β protein, impeding the protein’s ability to aggregate.
A new DNA data storage technology—data recording in vivo by electrical stimulation (DRIVES)—places CRISPR-based DNA encoding activity under electrochemical control by coupling cellular redox state to CRISPR array gene expression.
Single-molecule FRET of mGluR2 shows that the conformations of the ligand-binding domain and the linked cysteine-rich domain are loosely coupled during ligand-induced activation and defines two pre-active states linking inactive and active states.
Crystal structures of FEM1C in apo and in complex with a C-degron ending with arginine reveal a binding pocket in FEM1C that recognizes C-degrons and the essential role of C-terminal arginine for recognition.
Beginning with a functional site and building a supporting scaffold around it enables the de novo design of proteins with distinct binding motifs for use in biosensors to detect antibody responses and as ligands of synthetic signaling receptors.
Coupling light-inducible bacterial biofilm formation with hydroxyapatite mineralization enables the synthesis of living patterned and gradient composite biomaterials with control over the degree of mineralization and the ability to self-heal.
Using synthetic ubiquitins with non-natural acceptor site, the authors revealed that the length of lysine side chain in acceptor ubiquitins affects ubiquitin chain linkage specificity with native lysine as the preferred geometry.
Rather than their expected role in self-immunity, kinases encoded in the biosynthetic gene clusters of nucleoside natural products catalyze the phosphorylation of an early intermediate, a modification that is later removed in a downstream step.
Qemistree uses fragmentation spectra to predict molecular fingerprints and represent their relationships as a tree, enabling comparison of metabolomics data across different experimental conditions and exploration of chemical diversity in mixtures.
Native mass spectrometry, HDX-MS and MD simulations define the mechanism for how LPS binding to the Gram-negative outer membrane complex LptDE opens the LptD lateral exit gate and how thanatin impairs transport across the periplasm.
The authors identify the interaction between transcription factor YY1 and DNA G4 structures, which contributes to chromatin looping induced by YY1 dimerization as well as its transcriptional regulation.
Tryptolinamide (TLAM) is a small molecule compound that inhibits phosphofructokinase-1 activity and rescues the metabolic defects of patient-derived induced pluripotent stem cell lines with mutated mitochondrial DNA.
A two-cell setup containing tryptophanase, a flavin-dependent monooxygenase and a regiospecific halogenase (linked to a flavin reductase as a solubility tag) enables the production of 6,6'-dibromoindigo and other indigoid dyes in Escherichia coli.
The authors identified a pH-dependent protonated status in the miR-21 precursor, which leads to additional base pairing in its secondary structure, thus affecting Dicer processing and miR-21 maturation.
The helical bundle structure of the CC1 domain of STIM1 of the store-activated calcium channel CRAC is crucial to maintaining the channel resting state, and helix–helix interactions can be manipulated to normalize a disease-linked STIM1 mutant.
Redirecting plant diterpene biosynthesis from the chloroplast to the cytosolic, high-flux mevalonate pathway increases intermediate and product titers to support the elucidation and reconstitution of momilactone biosynthesis.
Structural and kinetic analyses of the transcriptional repressor SqrR in multiple states indicate that its persulfide selectivity is determined by structural frustration in the disulfide form, favoring formation of the tetrasulfide-bridged product.
Screening for substrate preference of the SARS-CoV and SARS-CoV-2 main protease Mpro leads to the development of activity-based probes useful for structural analysis and for visualization of active Mpro in infected patient epithelial cells.
A screening approach finds VH-domain antibodies that bind the SARS-CoV-2 Spike protein receptor-binding domain at its interface with host ACE2. Bi-paratopic and multivalent binders have high affinity and potency.
The plant cuticle was initially thought to act as a passive diffusion barrier. Genetic and metabolic analysis reveals that it is also a sink/concentrator for volatiles protecting cells from toxic effects of these hydrophobic compounds.
Increased production of (S)-reticuline and other alkaloids is achieved through alleviating norcoclaurine synthase toxicity by targeting the enzyme to the peroxisome plus enlarging peroxisomes by expression of engineered transcription factors.
A family of riboswitches named Sensei that specifically sense iron has been discovered and characterized, which enables the authors to engineer metal ion sensing riboswitches to convert their metal selectivity.
A chemical glycobiology approach reveals that heparan-sulfate glycosaminoglycans regulate vascular development through direct interactions with angiopoietin (Ang) ligands and the Tie1 receptor of the Ang–Tie signaling system.
Structural analysis of transcription activation complex comprising E. coli transcription factor CueR, RNAP holoenzyme and promoter DNA reveals that CueR distorts the DNA conformation to promote the association of promoter with polymerase.
The whitefly Bemisia tabaci defends against plant glucosinolate toxins by serial addition of glucose moieties catalyzed by a pair of glycoside hydrolases, preventing toxin activation during feeding on the plant tissue.
A fluorescence-based sensor of PKA activity has increased brightness, dynamic range and signal-to-noise ratio over related sensors and is useful for visualizing kinase activity in HeLa cells, primary neurons and the cortex of awake mice.
Native ion mobility mass spectrometry reveals two isoforms of the two-pore domain K+ channel K2P4.1 have distinct binding preferences for lipids and show a relationship between the strength of individual lipid binding events and channel activity.
A bifunctional AURORA-A degrader induces the fast and specific degradation of this kinase in cancer cell lines, which enables targeting of non-catalytic, oncogenic functions of AURORA-A resulting in S-phase arrest and rampant apoptosis.
Immunomodulatory drugs are used for the treatment of multiple myeloma. ARID2, a component of the PBAF chromatin-remodeling complex, is a new pomalidomide-induced neosubstrate of CRL4CRBN, which accounts for its superior efficacy over lenalidomide.
Imaging of phosphatidylcholine, sphingomyelin and their interorganelle lipid transport in live cells, using azido-choline and a spatially limited bioorthogonal tag, suggests that autophagosomal membranes originate from the ER.
Changes in O-GlcNAc levels controlled the actin contraction of fibroblasts in response to sphingosine-1-phosphate (S1P). Specifically, O-GlcNAc modification of the phosphatase MYPT1 maintains its activity to block S1P signaling.
Cryo-EM structural work shows sterols binding at four adjacent locations within the class F GPCR Smoothened (SMO), where the transmembrane core functions as a sterol tunnel in which occupancy activates SMO for downstream Hedgehog signaling.
Incorporation of the non-canonical amino acid 3-aminotyrosine into the chromophores of green fluorescent protein-based biosensors systematically red-shifts their fluorescent properties while maintaining brightness, dynamic range and responsiveness.
Reengineering of the lac operon in E. coli from a ligand-inducible to a blue-light-regulated gene expression system facilitates optogenetic control of biotechnological applications including metabolic engineering and protein expression.
Pyruvate-responsive circuits based on an orthologous transcription factor and adaptation of an antisense transcriptional circuit were developed to sense pyruvate in Bacillus subtilis and redirect metabolism for optimized glucaric acid production.
An irreversible small-molecule inhibitor of histone methyltransferase NSD1 is developed, which binds covalently to the C2062 residue in the catalytic SET domain and represses H3K36 dimethylation and target gene expression in leukemia cells.
A cell-free system for cannabinoid production uses only low-cost inputs with 12 enzymes and can operate either aerobically or anaerobically, in addition to reducing ATP requirements by use of an engineered system for malonate-CoA biosynthesis.
Structural and biochemical analysis of E. coli transketolase with 2′-methoxy-thiamine shows that this antivitamin selectively inhibits the bacterial enzyme via a steric clash with a critical glutamate residue, preventing cofactor activation.
Cryo-EM structural work defines binding of the insecticide CHL in the pseudo-voltage-sensor domain of ryanodine receptor RyR that triggers conformational changes leading to channel opening and explains the resistance to CHL by some insects.