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  • 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.

    • Jesse D. Gelles
    • Jerry Edward Chipuk
    News & Views
  • A proteomics and computational approach was developed to map the proximal proteome of the activated μ-opioid receptor and to extract subcellular location, trafficking and functional partners of G-protein-coupled receptor activity.

    • Benjamin J. Polacco
    • Braden T. Lobingier
    • Ruth Hüttenhain
    Article
  • 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.

    • Ninian J. Blackburn
    News & Views
  • Huang et al. developed E3-substrate tagging by ubiquitin biotinylation (E-STUB), a proximity labeling-based method for direct identification of ubiquitylated substrates for a given E3 ligase, providing a useful tool for substrate discovery of targeted protein degradation and the understanding of E3 ligase function.

    • Hai-Tsang Huang
    • Ryan J. Lumpkin
    • William R. Sellers
    Article
  • Hypoxia induces ·NO-dependent hydrogen sulfide (H2S) biogenesis by inhibiting the transsulfuration pathway. H2S oxidation promotes endothelial cell proliferation to support neovascularization in tissue injury and tumor xenograft models.

    • Roshan Kumar
    • Victor Vitvitsky
    • Ruma Banerjee
    Article
  • An approach to design proteins that can capture amyloidogenic protein regions present in, for example, tau and Aβ42 has now been developed. These designer proteins can inhibit the formation of pathogenic amyloid fibrils and protect cells from toxic species.

    • Danny D. Sahtoe
    • Ewa A. Andrzejewska
    • David Baker
    ArticleOpen Access
  • 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.

    • Vincent Courdavault
    • Nicolas Papon
    News & Views
  • The study demonstrates that specific recognition and custom binding geometries can be computationally encoded between protein spans within lipids through designing synthetic transmembrane proteins to functionally regulate a target cytokine receptor.

    • Marco Mravic
    • Li He
    • William F. DeGrado
    ArticleOpen Access
  • 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.

    • Ya-Ming Hou
    • Yuko Nakano
    News & Views
  • NMR and Raman spectroscopies pinpoint the role of the protein droplet surface and RNA in the liquid droplet maturation mechanism of the FUS protein. A crust-like β-sheet structure is formed on the surface of FUS droplets during aging.

    • Leonidas Emmanouilidis
    • Ettore Bartalucci
    • Frédéric H.-T. Allain
    ArticleOpen Access
  • The rate of ATP production and the total mass of enzymes were quantified for both glycolysis and mitochondrial respiration to determine the proteome efficiency of these pathways. Per unit of enzyme mass, mitochondrial respiration generates energy faster than glycolysis and is thus more proteome efficient. Despite being less proteome efficient, constitutive glycolysis comes with the benefit of rendering cells robust to hypoxia.

    Research Briefing
  • AlphaFold is a breakthrough in protein structure prediction, but limitations in its application to computation- and structure-guided drug discovery remain. As with structure prediction, public-domain data and benchmarking initiatives will be essential to advance the field of computational drug design.

    • Matthieu Schapira
    • Levon Halabelian
    • Rachel J. Harding
    Comment
  • 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.

    • Jerod S. Denton
    News & Views