Volume 18 Issue 10, October 2022

The Hippo pathway is a key regulator of tissue homeostasis, organ size and cancer. Identification of microcolin B and its analog molecules as Hippo pathway activators connects PtdIns4P-dependent lipid signaling with the Hippo pathway, suggesting potential targets for cancer therapy.

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.

Single-molecule methods are a powerful tool to study the kinetics of ATP-powered enzymes. A method that locally controls the generation of ATP significantly increases the throughput of single-molecule approaches and unlocks single-turnover analysis of molecular machines.

A redesigned antiviral miniprotein based on a dimeric helix-hairpin motif binds and dimerizes the RBD of the SARS-CoV-2 spike protein and inhibits viral infection by inhibiting spike interaction with ACE2.

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.

Aldehyde dehydrogenase 1B1-specific small-molecule inhibitors are identified that block the growth of colon cancer spheroids and organoids and are shown to potentially regulate mitochondrial metabolism and ribosomal function.

The marine compound microcolin B stimulates the Hippo pathway and selectively kills YAP-dependent cancer cells by inhibiting phosphatidylinositol transfer protein and depleting plasma membrane phosphatidylinositol-4-phosphate.

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

Functional screening of a large metagenomic library with a droplet microfluidics platform enabled the discovery of SN243, a bacterial β-glucuronidase from the glycoside hydrolase 3 family, which was characterized structurally and biochemically.

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

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.

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.

Bicyclostreptins are peptide natural products in which a macrocyclic β-ether and a heterocyclic sp³–sp³ linkage between a backbone amide nitrogen and an adjacent α-carbon are installed by two radical S-adenosylmethionine metalloenzymes.

A new method for controlling NTP-driven reactions in single-molecule experiments via the local generation of NTPs (LAGOON) markedly increases the measurement throughput and enables single-turnover observations.

Using methyl group and fluorine NMR spectroscopic methods, Overbeck et al revealed that the dynamics of the eukaryotic 5′→3′ exoribonuclease Xrn2 in the region around the active site are correlated with its catalytic activity.