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  • A newly developed maternally selective nanobody antagonist against the angiotensin II type I receptor stabilizes the receptor in a hybrid conformation and simultaneously binds with specific small-molecule antagonists.

    • Meredith A. Skiba
    • Sarah M. Sterling
    • Andrew C. Kruse
  • Biochemical pathways for aromatic amino acid synthesis are ancient and highly conserved. Directed evolution of the β-subunit of tryptophan synthase (TrpB)—a proficient biocatalyst that converts indole to l-tryptophan—enabled this enzyme to make l-tyrosines from phenols, a pathway not (yet) known in nature.

    • Patrick J. Almhjell
    • Kadina E. Johnston
    • Frances H. Arnold
  • Natural ribozymes can cleave RNA and single-stranded DNA (ssDNA) by transesterification or a blend of hydrolytic and transesterification reactions. Now, ribozymes have been discovered that catalyze the hydrolytic cleavage of ssDNA. Similar ribozymes could potentially replace large, immunogenic, protein-based nucleases in gene therapies.

    • Madeleine B. King
    • Audrone Lapinaite
    News & Views
  • Ferroptosis, a cell death mechanism induced by lipid peroxidation, is pivotal in tumor suppression. A recent study shows that tumor repopulating cells evade ferroptosis and develop resistance to therapy via subverting a lipid metabolism enzyme.

    • Yuelong Yan
    • Boyi Gan
    News & Views
  • We present a discovery pipeline integrating chemical fragment screening and time-resolved, high-throughput small-angle X-ray scattering (TR-HT-SAXS). This approach identifies allosteric chemical leads targeting distinct allosteric states of the mitochondrial oxidoreductase apoptosis-inducing factor (AIF). By monitoring kinetic rates of allosteric transition with TR-HT-SAXS, we link fragment structure–activity relationships (SARs) to biomolecular conformation.

    Research Briefing
  • CRISPR–Cas13 systems use single-subunit RNA-guided Cas13 effectors for targeted RNA recognition and cleavage. This Review summarizes the recent advances in understanding the structural and mechanistic aspects of Cas13 systems and the diverse applications of these systems in biotechnology and therapeutics.

    • Hui Yang
    • Dinshaw J. Patel
    Review Article
  • Understanding the role of pyrophosphorylation requires specific analytical strategies to discriminate it from protein phosphorylation. A custom workflow reveals that nucleolar protein pyrophosphorylation in human cells regulates the transcription of ribosomal DNA.

    • Claire E. Eyers
    • Christopher J. Clarke
    News & Views
  • A tailored proteomics workflow to identify endogenous protein pyrophosphorylation in human cells was developed, revealing the dependence of the modification on inositol pyrophosphates and a putative function in rDNA transcription.

    • Jeremy A. M. Morgan
    • Arpita Singh
    • Dorothea Fiedler
    ArticleOpen Access
  • Cryo-electron microscopy (cryo-EM), kinetic analysis and single-molecule biochemistry reveal how the tubulin tyrosine ligase-like 6 (TTLL6) glutamylase binds reads microtubule geometry and modification state of neighboring tubulins, enabling a spatial positive feedback loop for microtubule modification.

    • Kishore K. Mahalingan
    • Danielle A. Grotjahn
    • Antonina Roll-Mecak
  • Calcium signals are typically traced through electrophysical, optical and genetic methods. Here the authors report the development of Cal-ID, a calcium-dependent protein proximity labeling tool that can be used to record elevated calcium levels in cells.

    • J. Wren Kim
    • Adeline J. H. Yong
    • Nicholas T. Ingolia