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  • The gut microbiota has a key role in protecting hosts from pathogens. A new study identified a gut microbiota-derived bile acid (chenodeoxycholic acid) that inhibits bacterial infection by interacting with a regulatory protein necessary for the expression of virulence factors.

    • Deyanira Pérez-Morales
    • Víctor H. Bustamante
    News & Views
  • 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.

    • Jens C. Schmidt
    News & Views
  • Isoform-selective inhibition of JAK kinases is of key interest in drug discovery. A novel pocket in the JAK pseudokinase domain was targeted by an allosteric covalent inhibitor, leading to specific JAK1 inhibition and providing a deeper understanding of cytokine signaling.

    • Olli Silvennoinen
    • Teemu Haikarainen
    • Anniina Virtanen
    News & Views
  • Elucidating the interactions between serum protein-bound nanoparticles and cell-surface receptors typically operates on a per protein–receptor interaction basis. Integration of omic approaches for testing thousands of interactions unbiasedly reveals important interactions that drive cellular uptake of nanoparticles.

    • Cecilia Ka Wing Chan
    • Sze Ho Gwyneth Lau
    • Chung Hang Jonathan Choi
    News & Views
  • 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.

    • Beomjong Song
    • Sangsu Bae
    News & Views
  • 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.

    • Lauren Waters
    News & Views
  • 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.

    • Kamran Rizzolo
    • Diana M. Mitrea
    News & Views
  • 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.

    • Alexander Leitner
    News & Views
  • 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.

    • Micah J. Niphakis
    • Benjamin F. Cravatt
    News & Views
  • A directed evolution approach delivers ribosomes with highly functional tethered subunits. Combining the decoding and peptidyl transferase activities of the ribosome into a single entity sets the scene for more efficient protein engineering technologies.

    • Aleksandra Filipovska
    • Oliver Rackham
    News & Views
  • 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.

    • Gayoung Seo
    • Wenqi Wang
    News & Views
  • 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.

    • Tatiana J. Rosales
    • Brian M. Baker
    News & Views
  • Carbon dioxide (CO2) is a product of cellular respiration that can also serve as a post-translational modification (PTM) through covalent protein modification. A new chemoproteomic strategy enables the capture of functional CO2-dependent carboxylation on lysine residues of proteins.

    • R. Justin Grams
    • Ku-Lung Hsu
    News & Views
  • The rising threat of antifungal resistance means that alternative therapeutics need to be considered. New research explores the biochemical basis of virulence inhibition by mucus glycans against the fungal pathogen Candida albicans.

    • Jehoshua Sharma
    • Rebecca S. Shapiro
    News & Views
  • A fungal ten-eleven translocation (TET) dioxygenase homolog, CcTet, is found to have both 5-methylcytosine (5mC) and N6-methyladenine (6mA) demethylase activity. Structure-based engineering of CcTet yielded a 6mA-specific demethylase, offering a useful tool for the manipulation and functional study of 6mA.

    • Sisi Li
    • Jiamu Du
    News & Views
  • The discovery of long-existing terpenoid biosynthetic pathways in soft corals changes the way specialized metabolism in animals is thought about, and opens unprecedented access to the largely untapped treasure trove of medicinal marine natural products.

    • Trinh-Don Nguyen
    • Thu-Thuy T. Dang
    News & Views
  • Controlling kinase inhibitors’ residence time via reversible covalent binding is of high interest in drug discovery. Tuning reversible covalent binding kinetics using a pan-kinase inhibitor that reacts with the catalytic lysine enabled exquisite temporal selectivity in vitro and in vivo.

    • Fleur M. Ferguson
    News & Views
  • 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.

    • Nivine Srour
    • Stéphane Richard
    News & Views
  • Natural enzyme complexes can rapidly change configurations to respond to intracellular cues. Now CRISPR enzymes and programmable RNA scaffolds allow synthetic enzyme complexes to be assembled and disassembled on demand.

    • Alexander A. Green
    News & Views
  • Microproteins can be generated by a shift in the reading frame during translation. A chemoproteomics approach led to the identification of MINAS-60 as an alternative microprotein that regulates the assembly of the pre-60S ribosome.

    • Valdeko Kruusvee
    • Stephan Wenkel
    News & Views