News & Views

Versatile methods for rapid, reversible and repetitive control of protein localization are lacking. A novel optically controlled dimerization system enables precise control of subcellular protein localization while retaining compatibility with multicolor fluorescence microscopy.

Natural products and synthetic bifunctional molecules enable the development of new chemical probes that target oxysterol-binding protein (OSBP), a key player in intracellular cholesterol homeostasis and Golgi complex integrity and a potential target for metabolic disease and cancer.

Identifying the protein component of calcium signaling in specific subcellular regions presents considerable challenges. Researchers have now successfully integrated calcium indicators with proximity labeling, enabling the targeting of microdomain-specific calcium signaling.

An in vivo chemical screen has uncovered a potential role for a tryptophan metabolite in promoting host survival during bacterial infections through modulation of ionotropic glutamate receptors. Host-directed therapies for bacterial infections offer a largely untapped approach to treatment.

To understand the complex dynamics and diverse functions of RNA, robust technologies for labeling and imaging RNA are highly desirable. A newly developed green fluorescent aptamer named Okra enables the imaging of mRNA dynamics in living cells.

The ZDHHC family of palmitoyl transferases lipidates numerous protein targets, but the paucity of selective inhibitors has hindered their target profiling. A generalized chemical genetic system can now map the protein targets of individual ZDHHC family members.

Targeted protein degradation has emerged as a promising approach in drug discovery, harnessing a cell’s intrinsic machinery to eliminate disease-related proteins. Now, a study paves the way to translating this technology into potential anti-mycobacterial therapies, by exploiting the bacterial protein-degradation complex.

Reliably identifying ubiquitin ligase interactors and substrates has been a persistent challenge in cellular biology. A breakthrough comes in the form of a potent, selective and cell-active chemical probe, shedding light on the intricate functions of a key regulatory enzyme.

Natural ribozymes can cleave RNA and single-stranded DNA (ssDNA) by transesterification or a blend of hydrolytic and transesterification reactions. Now, ribozymes have been discovered that catalyze the hydrolytic cleavage of ssDNA. Similar ribozymes could potentially replace large, immunogenic, protein-based nucleases in gene therapies.

Ferroptosis, a cell death mechanism induced by lipid peroxidation, is pivotal in tumor suppression. A recent study shows that tumor repopulating cells evade ferroptosis and develop resistance to therapy via subverting a lipid metabolism enzyme.

Understanding the role of pyrophosphorylation requires specific analytical strategies to discriminate it from protein phosphorylation. A custom workflow reveals that nucleolar protein pyrophosphorylation in human cells regulates the transcription of ribosomal DNA.

Ribosomally synthesized and post-translationally modified peptide (RiPP) natural products typically rely on substrate recognition through remote protein–protein interaction sites. Now, an atypical dehydratase, whose activity is directed by neighboring azole modifications, has been shown to produce a highly modified peptide hybrid bearing dehydroamino acids, enabling the synthesis of members of the dehydrazole family of RiPPs.

Reprogramming intercellular mechanotransduction and signaling pathways is still challenging. A recent advance uses a plug-and-play DNA nanodevice to allow non-mechanosensitive receptor tyrosine kinase (RTK) to transmit force-induced cellular signals.

Peptide vaccines use antigenic peptide fragments to induce an immune response but are problematic because of the short half-life of peptides. A study now reports thioamide substitution in the peptide backbone as a strategy to enhance resistance to proteolysis and promote binding to the MHC I complex for T cell activation.

Detection of intracellular lipolysaccharide (LPS) activates an immune response initiated by the non-canonical inflammasome. ATGL has now been identified as a negative regulator of this pathway that dampens inflammation by removing LPS’ acyl chains, preventing the activation of inflammatory caspases and cytokines.

Chemogenetic profiling can reveal genetic determinants that coordinate phenotypic responses to therapeutics, along with predicting potential pathways of resistance. A new analytical method for evaluating chemogenetic profiles reveals contributions from death-regulatory genes.

BURP-domain proteins belong to an emerging class of autocatalytic copper-containing proteins that modify themselves after synthesis. Now, a report explains how their structure and metal coordination sphere control the installation of crosslinks within the core peptide, and shows how nature leverages mechanistic paradigms to create diversity.

An integrative approach has now enabled elucidation of the complete biosynthetic pathway of a prominent saponin adjuvant. Reconstruction of the whole biosynthetic pathway in a heterologous host provides new perspectives for the biotechnological supply of this immunostimulant.

Reprogramming of the genetic code allows the synthesis of proteins using new building blocks, thus opening the door to the development of a wider variety of medicines and biocatalysts; however, it is currently limited to α-amino acids. A new study has now reported the incorporation of β-linked and α,α-disubstituted monomers into a ribosome-synthesized protein.

Kir4.1 potassium channels expressed in astroglial cells critically regulate extracellular potassium concentration in the brain. A new study reports that blocking the flow of potassium ions into astrocytes by inhibiting Kir4.1 induces rapid-onset antidepressive effects in rodents.