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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 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.