Research articles

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.

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.

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.

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.

Here, the authors show that the complete set of the Atg8–E1–E2–E3 conjugation machinery forms an interaction web through multivalent weak interactions, which mediates membrane shaping observed during autophagosome formation.

Here, the authors describe 3D hubs as regulatory subunits of gene expression in the three essential lineages of embryogenesis. They develop a computational model that can predict novel enhancers and they validate such enhancers in the context of specific lineages.

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.

Here, using CAGE-seq, the authors show that transcription start site choice in thousands of genes may endow transcripts with distinct post-transcriptional fates, with dynamic switching defining cancer cell proliferation, differentiation and treatment response.

Here the authors show that, in the absence of Pi3K–AKT–mTOR signaling, AGO2 accumulates in the nucleus of quiescent cells, where it binds to young retrotransposons and represses their expression.

Mao et al. reported ribosomal frameshifting events shortly after start codon selection, which is influenced by the sequence context and controlled by initiation factor eIF5B. This translational ‘noise’ is increased in response to nutrient starvation.

Extensive mutational analyses of ferroptosis suppressor protein-1 (FSP1) reveal its molecular mechanism in ferroptosis prevention and uncover the mechanism of action of the FSP1 inhibitor iFSP1 and a new species-independent FSP1 inhibitor, viFSP1.

Many multipass membrane proteins are not fully inserted into the membrane when translation ends. Wu et al. now show that a membrane insertase called EMC can facilitate maturation of these proteins by post-translationally completing their insertion.

Cryogenic electron microscopy structures reveal how the immunophilin co-chaperones, FKBP51 and FKBP52, each engage Hsp90–client complexes to directly stabilize a folded, ligand-bound client, the glucocorticoid receptor, and promote the next stage of client maturation.

Braxton et al. report structures of human p97/VCP bound to the UBXD1 adaptor involved in autophagy. The structures reveal how UBXD1 utilizes multiple interaction domains to remodel and open the hexamer ring, revealing its role in p97 regulation.

The authors reveal the architecture and functional annotation of large immunophilin-containing Hsp90–apo-GR complexes by systematic incorporation of photocrosslinker inside human cells and show that FKBP51 and FKBP52 differentially interact with the apo-GR.

Using cryo-EM, here the authors structurally delineate the Elongin–RNA polymerase II holocomplex. They show that Elongin allosterically regulates the transcribing RNA polymerase II via a latch that affects its conformational mobility.

The authors show that the lncRNA-derived microprotein SMIMP, which is shown to promote tumor formation, regulates cohesin core subunit binding to cis-regulatory elements and alters the expression of tumor-suppressive cell cycle regulators.

Here, Kasaragod et al. solve structures of the GABA_A receptor α5 subunit in complex with different classes of positive and negative allosteric modulators to explain the binding modes and the molecular basis of selectivity.

This study revealed the mechanism by which the E3 ligase Bre1 directs monoubiquitination of histone H2B at K123 by the E2 ubiquitin-conjugating enzyme Rad6. Comparison with other dimeric E3 ligases suggests a pivot-like mechanism in which one subunit ‘tunes’ the specificity for particular histone residues.

Here, using single molecule experiments, the authors show that the mechanical stability of cohesin encircling DNA is determined by its hinge domain that disengages at ~20 pN force, providing a framework for how cohesin counteracts spindle-generated tension during mitosis.