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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.
A chemical screen targeting major epigenetic pathways identifies permissive epigenetic states that enable reprogramming with a broad range of transcriptional regulators and almost all octamer-binding (OCT) family members.
The interaction between E1 and E2 is targeted by a stapled peptide that mimics the alpha-1 helix of E2, resulting in blockade of ubiquitin transfer from E1 to E2.
Structural and biophysical approaches suggest that structural preorganization is important for triggering endogenous CD8+ T cells and escape from immune tolerance, as demonstrated by a single nonsynonymous mutation in an ovarian cancer neoepitope
Application of an electrical field to Geobacter sulfurreducens biofilms stimulates production of OmcZ nanowires, which undergo a pH-induced conformational switch that causes increased stiffness and conductivity due to enhanced heme group π-stacking.