Volume 18 Issue 8, August 2022

Protein arginine methyltransferases (PRMTs) are overexpressed in many cancer types, including triple-negative breast cancer (TNBC). A new study shows that a reversible inhibitor of type I PRMTs suppresses TNBC tumor growth by inducing a viral mimicry response with retained introns.

Antigen loading onto class I major histocompatibility complex (MHC-I) proteins relies on chaperones and protein flexibility. Researchers now provide new insight into the process, especially for the intriguing ‘non-classical’ MHC-I protein MR1, with implications for fundamental immunology and the development of novel immunotherapies.

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.

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.

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.

Lechner et al. used an affinity-based chemical proteomics approach to investigate the target landscape of HDAC inhibitors, and identified an extracellular vesicle regulator MBLAC2 as a universal off-target of 24 hydroxamate inhibitors.

Type I PRMT inhibition elicits potent antitumor activity associated with increased interferon response and intron-retained dsRNA accumulation, suggesting its potential combination with immune checkpoint inhibitors for cancer treatment.

The crystallographic and cryo-EM structures of CB1 bound to the positive allosteric modulator ZCZ011, combined with molecular dynamics simulations and mutagenesis experiments, reveal allosteric modulation of CB1 by rearrangement of the TM2 and TM3 transmembrane domains.

Comprehensive structural biology analysis of seven members of the S1 carbohydrate sulfatase family derived from human gut microbiome Bacteroides reveals mechanisms of glycan recognition and sulfate hydrolysis.

A new targeting modality-based transcellular labeling technology called photocatalytic cell tagging enables monitoring of cell–cell interactions when combined with multiomics single-cell sequencing.

Biochemical and structural approaches define how the chaperone TAPBPR interacts with MR1 molecules, including empty and ligand-loaded MR1, and facilitates presentation of metabolite-derived antigen ligands by MR1 complexes.

The zinc-sensor protein Zur in a marine cyanobacterium is distinct from those in other bacteria in structure and location of its sensory zinc site, and facilitates growth across a range of zinc concentrations via activation of a metallothionein gene.

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.

A combination of engineering a fluorine-selective trans-acyltransferase and manipulation of the fluorinated extender unit pool in Escherichia coli enables the production of site-selectively fluorinated erythromycin precursors in vitro in vitroin vitro and in vivo.

Using nanobodies labeled with FRET fluorophores, the authors show the presence and activation of GPCR mGlu2 and mGlu4 dimers in mouse brain samples and reveal that mGlu2–mGlu4 is the major form of mGlu4-containing dimers outside the cerebellum.

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.