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  • Using cryo-EM, Schmidt, Schulz, et al. solve the structure of the iron nitrogenase complex, which shows a unique architecture of alternative nitrogenases and suggests the G subunit to be involved in substrate channeling, stabilization of the cofactor and determining specificty among nitrogenase components.

    • Frederik V. Schmidt
    • Luca Schulz
    • Johannes G. Rebelein
    ArticleOpen Access
  • The study presents a high-resolution structure of the retriever complex and a model of the retriever–CCC assembly, providing a mechanistic framework for studying how retriever facilitates endosomal recycling of diverse membrane proteins.

    • Daniel J. Boesch
    • Amika Singla
    • Ezra Burstein
  • The formation of the 2′–5′ lariat bond during branching is the critical first step in RNA splicing. A structure of a group II intron reveals a conserved base triple responsible for positioning the adenosine nucleophile to attack the 5′ splice site.

    • Daniel B. Haack
    • Boris Rudolfs
    • Navtej Toor
  • Here, cryo-electron microscopy structures of sodium–glucose cotransporter 2, which is responsible for sugar reabsorption in the kidney and is a target for the treatment of type 2 diabetes, reveal a potential mechanism for cellular sugar uptake.

    • Masahiro Hiraizumi
    • Tomoya Akashi
    • Ikuko Miyaguchi
    ArticleOpen Access
  • Transcription factors are rich in intrinsic disorder and therefore hard to drug. The authors improve an experimental drug for castration-resistant prostate cancer by learning how the activation domain of the androgen receptor activates transcription.

    • Shaon Basu
    • Paula Martínez-Cristóbal
    • Xavier Salvatella
    ArticleOpen Access
  • We describe how transcription start site (TSS) choice of thousands of genes results in transcript isoforms with potential for distinct post-transcriptional regulation affecting translation and cell behavior. We show that dynamic switching between initiation sites defines cancer proliferation, differentiation and treatment response, indicating start site determination as a potential diagnostic tool.

    Research Briefing
  • DNA polymerase θ (POLQ) repairs mitotic DNA breaks; this requires RHINO and PLK1, averts genomic instability and may underlie effects of POLQ inhibitors in HDR-deficient cancer cells. We discuss recent work on mitotic DNA break processing and repair, the need for multiple DSB repair pathways and implications of therapeutic POLQ targeting in cancer.

    • Marcel A. T. M. van Vugt
    • Marcel Tijsterman
  • An Ago2HA/HA mouse model combined with super-resolution microscopy, molecular and biochemical assays allowed us to stringently characterize AGO2 regulation in vivo. We found that in quiescent splenocytes, AGO2 localizes almost exclusively to the nucleus, where it binds to the RNA of young mobile transposons and represses their expression through its catalytic domain.

    Research Briefing
  • The human ATPase p97 (also known as VCP) unfolds protein substrates by translocating them through its central channel. This process is highly regulated by numerous adapter proteins. Structures of p97 in complex with the unusual adapter UBXD1 reveal how this protein coordinates p97 hexamer remodeling and ring opening by expansive interactions across multiple p97 protomers.

    Research Briefing
  • Ferroptosis suppressor protein 1 (FSP1, or AIFM2), an NADPH quinone reductase noted to protect cancer cells from ferroptosis, acts in FAD/NADPH binding and proton transfer. Recent papers assess its evolutionarily conserved sites via mutagenesis and define its inhibition as an off-target mediator of brequinar-mediated ferroptosis sensitization.

    • Christina M. Bebber
    • Silvia von Karstedt
    News & Views
  • OAT1 has a fundamental role in the kidney by facilitating the urinary excretion of various drugs and endogenous metabolites. Two studies now present high-resolution structures of OAT1 using cryo-EM, elucidating its intricate polyspecific transport capabilities and paving the way for structure-based drug research and development.

    • Leifu Chang
    News & Views