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Merging the generalized extracellular molecule sensor (GEMS) system with screening designed ankyrin repeat proteins (DARPins) identifies an advanced modular bispecific extracellular receptor (AMBER) for detection of fibrinogen degradation products.

A FRET-based assay using the conserved tryptophans of bacterial quorum-sensing LuxR-type proteins and synthetic fluorophore-acyl-homoserine lactone conjugates enables measurement of ligand-binding affinities either in vitro or in cells.

Transposon-associated transposase B (TnpB) is the putative ancestor of Cas nucleases. A TnpB-based adenine base editor has now been developed that is small enough to be loaded into a single AAV vector without compromising editing activity.

A hypercompact adenine base editor termed TaRGET-ABE was developed by fusing a catalytically inactive transposon-associated transposase B guided by an engineered RNA to deaminases, which achieves efficient A-to-G conversions via adeno-associated viral delivery in mammalian genomes.

Emerging evidence shows that ubiquitination can occur on nonlysine residues and nonproteinaceous substrates. This perspective summarizes the recent discoveries in noncanonical ubiquitination and advocates the development of chemical biology tools for new substrate identification and mechanistic dissection.

In the post-genomic era, many genes and regulatory elements remain uncharacterized, including riboswitches — RNA structures that control gene expression by directly binding metabolites. Here, a new type of metal-responsive riboswitch that senses sodium cations expands the bacterial Na⁺ metabolic repertoire.

Only one protein factor is known that senses Na⁺ and controls gene expression. The Breaker Laboratory describes a bacterial riboswitch class selective for Na⁺ that regulates genes important for Na⁺ homeostasis, pH maintenance, osmotic stress response and ATP synthesis.

Using a Cas13d-based nanosystem to knockdown lung protease cathepsin L, Cui et al. demonstrated that CRISPR–Cas system can be used to prevent and treat SARS-CoV-2 infection by targeting mRNA of host genes.

Kras activation in pancreatic cancer cells induced O-GlcNAc modification of malate dehydrogenase 1, regulating glutamine metabolism and promoting tumor growth.

Biomolecular condensates form and dissolve in response to a wide range of signals. A new study reports a solubility-based phosphoproteome-profiling approach, which uncovers the extensive role of phosphorylation in regulating protein partitioning into condensates across the human proteome.

Chemical probes are powerful tools for the discovery of ligand-binding and drug-target sites on proteins. A new software helps to profile their performance in chemoproteomic applications.

Mutant-selective KRAS-targeting drugs hold great promise for the treatment of some of the most aggressive forms of cancer. Building on the breakthrough success of KRAS-G12C inhibitors, researchers have now found a way to target another mutant KRAS with serine-modifying covalent inhibitors.

A combination of solubility proteome profiling with phosphoproteomics enables systematic analysis of the phosphorylation status of proteins in soluble and condensate-bound pools.

pChem is a computational tool that provides a pipeline for performance assessment of chemoproteomic probes, with the ability to score the profiling efficiency, modification homogeneity and proteome-wide residue selectivity of a tested probe.

The discovery of a strained β-lactone electrophile that covalently targets a KRAS G12 somatic mutation and acylates the mutant serine to suppress oncogenic signaling.