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Chimeric antigen receptor T cells (CAR-T cells) are often hindered by the concurrent challenges of variable antigen expression patterns and immunosuppressive tumor microenvironments. A new approach enhances CAR-T cells by coexpressing bacterial enzymes that activate prodrugs in high concentrations at the disease site.
Optogenetic and thermogenetic tools have been limited to applications for single-state control of cellular processes. A single-component optogenetic tool was found to act as both a temperature sensor and a photoreceptor, enabling multi-state control of developmental signaling.
Reliable quantification and tracing of RNA molecules remain challenging goals. A new fluorescent RNA tag, developed based on a natural adenine-sensing riboswitch and named Squash, offers superior imaging properties and accurate quantification in living cells.
The design of biological materials with tunable properties is an emerging challenge for the twenty-first century. A new approach to direct engineered cells to stick together improves biomaterial performance and simplifies self-healing.
To avoid strife at the interface of basic carbon and nitrogen metabolism, Bacillus subtilis has developed a rather combative solution. If needed, its glutamate synthase suppresses conflicting glutamate breakdown by directly binding and immobilizing its metabolic opponent, glutamate dehydrogenase.
The molecular mechanism through which chromatin-bound RNA-binding proteins (chrRBPs) control transcription remains obscure. A new study reveals that chrRBPs can compartmentalize RNA and transcription machinery into a phase-separated condensate, thus modulating gene expression.
Structural biology and resistance analyses reveal the binding mode and the basis for selective inhibition of the ATP synthase rotary motor protein by glycosylated macrolides.
An autocatalytic peptide cyclase defines a new subclass of plant ribosomally synthesized and post-translationally modified peptides (RiPPs). This discovery explains the origins of a large family of cyclic peptides and inspires new tools for mining these RiPPs across the plant kingdom.
Chemoproteomics-enabled identification of the targets of a hydroxylated cholesterol metabolite, 20(S)-hydroxycholesterol, reveals it to be the first reported endogenous ligand of the sigma-2 receptor, a drug target for neurodegeneration and neuropathic pain.
Genetic code expansion is emerging as a promising strategy to precisely regulate protein expression. A new study engineered cells that enabled noncanonical-amino-acid-triggered insulin expression to rapidly regulate blood glucose levels in a diabetic mouse model.
A new study demonstrates that the receptor-binding domain of the SARS-CoV-2 spike protein binds to sialylated glycans, especially glycolipids, to facilitate viral entry, an insight that identifies new potential targets for SARS-CoV-2 interventions.
RNA modifications are emerging regulators of development and disease. A metabolic labeling approach using 5-fluorocytidine (5-FCyd) allows the mechanism-based profiling of several RNA-modifying enzymes and potentially links their activity to novel RNA targets.
Controlled positioning of the mitotic spindle is key to tissue development and homeostasis. A recent study uncovered an EB1 crotonylation event that orchestrates microtubule dynamics in late mitosis, thus ensuring correct division orientation in vertebrate cells.
Prokaryotic genomes are rife with highly similar toxin–antitoxin modules that need to be protected and diversified at the same time. Studies of paralogous modules now reveal how evolution secures insulation between related systems, without compromising toxin inhibition.
Targeting cholecystokinin receptors (CCKRs) signaling has become an attractive therapeutic strategy for many diseases. The description of cryo-EM structures of CCKRs in the active or inactive states reveal the molecular mechanism of ligand recognition and G-protein-coupling promiscuity.
Graspetides are an important class of ribosomal natural products with potent bioactivities. New structural information provides insights into substrate recognition and catalysis, including a rare glimpse into the interactions between a tailoring enzyme and the core of the precursor peptide.
LYTACs induce selective degradation of extracellular proteins by recruiting them to cellular receptors that mediate delivery to the lysosome. Recent development of GalNAc-LYTACs and MoDE-As targeting the liver-specific ASGPR enables cell-type-restricted lysosomal protein degradation and reveals new LYTAC design principles.
The structure of a giant ubiquitin E3 ligase sheds light on its activation in a substrate-dependent manner and shows how a single E3 enzyme uses distinct recognition modules to confer substrate specificity.
Liquid–liquid phase separation, yielding membraneless organelles, allows for the sequestration and functional insulation of cellular proteins. A modularly built, synthetic membraneless organelle platform enables efficient control over endogenous cellular activities by knockdown of protein function or controlled protein release.
