News & Comment

  • News & Views |

    The NLRP3 inflammasome contributes to pathogenic inflammation in a broad range of diseases, making it a highly relevant drug target. Two studies published in this issue found an inhibitor of NLRP3 inflammasome activation to directly bind NLRP3 within its central NACHT domain, interfering with ATP hydrolysis and structural changes critical for NLRP3 oligomerization and subsequent inflammasome formation.

    • Oliver Gorka
    • , Emilia Neuwirt
    •  & Olaf Groß
  • News & Views |

    Endocytosis mediates the internalization of proteins and lipids at the plasma membrane and plays essential roles in plant growth and development. A new small molecule enables manipulation of plant endocytosis in an acute and transient manner.

    • Chunhua Zhang
    •  & Glenn R. Hicks
  • News & Views |

    Chemical probes that irreversibly inhibit protein function may be used across species to discover proteins. Combining phenotypic screening and activity-based protein profiling, a new study uncovers a discrete lipid signaling pathway regulating lifespan in the worm Caenorhabditis elegans.

    • Jürg Gertsch
  • News & Views |

    Arginine protein kinases regulate bacterial signaling cascades through phosphorylation of key arginine residues. Crystal structures of the kinase McsB provide the first glimpse of how these unusual enzymes recognize their protein substrates and are allosterically regulated.

    • Titus J. Boggon
  • News & Views |

    The molybdenum cofactor (Moco) is a fragile prosthetic group essential for most organisms. Nematodes are now capable of extracting Moco from their bacterial diet to mediate detoxification of sulfite.

    • Ralf R. Mendel
    •  & Thomas W. Hercher
  • News & Views |

    The N6-methyladenosine modification next to the 5′ RNA cap has dynamic regulatory functions. Recent findings show that this modification regulates the splicing and translational activity of different classes of RNAs.

    • Richard A. Padgett
  • News & Views |

    Powerful combinatorial peptide library methods allow the discovery of peptide leads from diverse libraries. A new platform based on tandem mass spectrometry peptide sequencing coupled with high-performance size-exclusion chromatography enables identification of high-affinity peptidic ligands from focused libraries.

    • Kit S. Lam
  • News & Views |

    Potassium channels allow the passage of potassium ions across membranes at rates approaching the diffusion limit while maintaining exquisite selectivity between ion species. Single-molecule studies now reveal that the selectivity filter of these proteins transitions between different conformations.

    • Adrian Gross
  • News & Views |

    A small molecule was identified that binds to a unique site on the pro-apoptotic protein BAX, stabilizing the protein structure allosterically and preventing the conformational activation to a pore former by BH3 proteins.

    • Jialing Lin
  • News & Views |

    A new method introduces ubiquitin or ubiquitin-like proteins at specific sites in any protein without the requirement of the cellular ubiquitylation machinery. This will help decipher the code by which these modifications control cellular processes.

    • Amit Kumar Singh Gautam
    •  & Andreas Matouschek
  • News & Views |

    Cell envelope assembly during V snapping, an unusual method of cell division in Actinobacteria, is mechanistically different than that seen during cell division of many other bacteria.

    • Martin S. Pavelka Jr.
  • News & Views |

    Holliday junction resolvases lock dynamic DNA four-way junctions into specific structural conformations for symmetric DNA cleavage. Single-molecule studies now reveal that resolvases can relax their grip, enabling Holliday junction conformer transitions and branch migration in the enzyme-bound form.

    • Ulrich Rass
  • Research Highlight |

    • Grant Miura
  • News & Views |

    Faster-than-transcription control of cellular activities is an important but challenging engineering target. Using split ferredoxins and induced dimerization or conformational changes, newly developed metalloprotein switches provide a fast method to control electron flux.

    • Michaela TerAvest
  • News & Views |

    Two protein circuit systems, split-protease-cleavable orthogonal coiled-coil logic (SPOC logic) and circuits of hacked orthogonal modular proteases (CHOMP), have been developed to permit rapid and logic function-based control of mammalian cellular signaling.

    • Yiqian Wu
    •  & Yingxiao Wang
  • News & Views |

    The carboxyl-terminal domain (CTD) of RNA polymerase II (Pol II) is post-translationally modified during gene expression. A recent study has identified a CTD kinase, Hrr25, that regulates the termination of noncoding RNA genes by recruiting Rtt103, a key termination factor.

    • Carlos Mario Genes Robles
    •  & Frédéric Coin
  • News & Views |

    Characterization of a novel mutation in the E2 ubiquitin-conjugating enzyme UBE2A accounts for the decreased activity of the mutant enzyme that underlies disease and provides important insight into the catalytic mechanism of E2s.

    • Martina Foglizzo
    •  & Catherine L. Day
  • Editorial |

    Structural studies of GPCRs defining conformational states en route to activation and clarifying the mechanisms of activation, ligand bias, and signaling will be critical for discovering new drugs that target a range of diseases.

  • News & Views |

    Phase separation underlies the formation of cellular membrane-less organelles. A new report identifies deacetylation at lysine residues of intrinsically disordered protein regions to drive liquid droplet formation in vitro and stress granule maturation inside cells.

    • Alessia Ruggieri
    •  & Georg Stoecklin
  • News & Views |

    Prostanoids signal through G-protein-coupled receptors to regulate diverse physiological processes. Structures of three prostanoid receptors in inactive and active conformations now uncover the molecular determinants of ligand recognition and receptor activation and offer new opportunities for drug discovery.

    • Kaspar Hollenstein
  • News & Views |

    Terpenoids are assembled from five-carbon (C5) units, which limits the available scaffold chemical space for the discovery of bioactive molecules. A combination of enzyme and metabolic engineering now enables biosynthesis of a plethora of non-natural C11 terpenoids.

    • Yongjin J. Zhou
  • News & Views |

    Scientists have combined functional and computational analysis to predict the substrate specificity of a family of glycosyltransferases from Arabidopsis thaliana, creating a tool that enables researchers to classify the donor and acceptor specificity of glycosyltransferase enzymes.

    • Jochen Schmid