Articles

Nagano et al. identify the third mitotic cohesin complex, STAG3–cohesin, which, with its unique biophysical properties, weakens insulation and rewires regulatory interactions of spermatogonial stem cells, shaping the male germline nucleome.

Here, the authors describe a tubular module connecting oxidoreductases to the membrane. This system, found in many microorganisms, reveals a distinct mode of membrane anchoring and an electron transfer mechanism involved in energy conservation.

The authors present PIONEAR–seq technology to assay in vitro binding of pioneer transcription factors to nucleosomes. The PIONEAR–seq data reveal that a nucleosome’s broader sequence context regulates the interactions of pioneer transcription factors via DNA bendability.

Gangwar et al. present cryo-electron microscopy structures of GluK2 kainate receptors with auxiliary subunit Neto2 and reveal the basis of receptor activation.

Zaman, Yang and Huang et al. demonstrate MDK’s suppressive effect on amyloid-β and its impact on amyloid burden and microglial activation in Alzheimer disease mice, highlighting its protective role in pathogenesis.

Integrated structural biology approach leveraging in situ cryo-electron tomography reveals molecular details of the native malarial translation elongation cycle and its perturbation by cabamiquine, a potent antimalarial drug candidate.

Wang et al. show that pregnane X receptor (PXR), a well-known DNA-binding nuclear receptor, has mRNA stabilization functions when in the cytoplasm, thus unveiling a noncanonical perspective to understand and target PXR as an RNA-binding protein.

The authors reveal a three-domain architecture of glycoprotein clusterin and show that the hydrophobic tails are crucial for clusterin’s functions as an extracellular molecular chaperone and apolipoprotein, as well as for receptor binding and cellular uptake.

Using massively parallel splicing assays and mathematical modeling, Bonnal et al. uncover that conserved splice site strength and exon length encode microexon sensitivity to SRRM3 and SRRM4. This work revises the switch-like splicing regulation model into a dose-responsive continuum.

Gómez-Sánchez et al. show that generation of phagophore–endoplasmic reticulum exit sites (ERES) membrane contact sites, mediated by Atg2 and the TRAPPIII complex, triggers Ypt1 activation, which is a signal to initiate phagophore elongation.

The authors resolve high-resolution structures of complex multimeric RNA-only assemblies, redefining our understanding of non-coding RNA architecture and expanding the landscape of naturally evolved RNA nanostructures.

Single-molecular microscopy shows that GAGA multimeric zinc finger transcription factor searches chromatin for cognate sites through rapid one-dimensional sliding on free DNA (which can be blocked by nucleosomes) and three-dimensional diffusion for nucleosomal targets.

Wang, Kronenberg-Tenga, Rosti and colleagues use several structural approaches to analyze the distribution of nucleosomes at the lamin–chromatin interface, test the impact of lamins on nucleosome density and identify a lamin A nucleosome-binding motif.

Webb, Toporova and colleagues identify a β-hairpin motif in the kinesin-2 family, which controls motility by sequestering the motor domains from their microtubule track.

Using single-molecule analysis, the authors establish that direct competition between eIF1 and eIF5 governs accurate yet flexible translation initiation in humans, providing a biophysical framework with broad relevance to health and disease.

Jansen et al. determined the cryo-electron microscopy structure of human GTPase-activating protein complex GATOR2 bound to CASTOR1 in the absence of arginine, providing insight into how CASTOR1 binds to GATOR2 to disinhibit GATOR1 when arginine levels are low, promoting mechanistic target of rapamycin complex 1 inactivation.

Schrecker, Son and colleagues identify the accessory subunits transmembrane protein 9 (TMEM9) and TMEM9B for chloride transporters ClC-3, ClC-4 and ClC-5 and establish the roles of TMEM9 and phosphatidylinositol 3,5-bisphosphate in the regulation of ClC-3 activity and endosomal ion homeostasis.

Gene activity levels predict how often and how strongly genes turn on and off. Using live imaging in fruit fly embryos, the authors uncover a conserved rule linking transcriptional bursts to gene activity across time, space and species.

BiP–glucose-regulated protein 94 chaperones are critical to the proper folding of secretory and transmembrane proteins. Brenner et al. provide biochemical and structural insight into a conserved mechanism of chaperone cooperation underlying this quality control process.

Nardone et al. identify a metazoan protein complex (mRAVE) that assembles V-ATPases from two subcomplexes, enabling lysosome acidification, neurotransmitter vesicle loading and a lysosome damage response pathway.