Articles in 2025

Fu et al. uncover the features that allow the HIV capsid to cross the permeability barrier of nuclear pores in an importin-independent manner, explaining how the viral genome can reach the nuclear compartment when infecting nondividing cells.

Here Schwämmle et al. develop CRISPR reporter screens to map transcription-factor-regulatory element interactions at the Xist locus, revealing a two-step mechanism integrating developmental and X-dosage signals to initiate X-chromosome inactivation.

Issa et al. show that the ciliary small guanosine triphosphatase Arl3 displaces the inhibitory regulator Shulin/DNAAF9 from the outer dynein arm, leading to motor activation.

This study reveals how human small ubiquitin-like modifier (SUMO) E1 recruits its E2 partner UBC9 and transfers SUMO1 through large structural changes, uncovering key mechanisms that ensure specificity and fidelity in SUMOylation, an essential protein modification pathway.

Many mutations cause disease because they destabilize proteins. Here, Mighell and Lehner show that a single small molecule can correct the destabilization caused by nearly all pathogenic mutations in a human GPCR.

By studying dynamic folding intermediates on the human ribosome, Pellowe et al. show that newly made domains help each other to fold but do not stably interact until synthesis is complete, avoiding interdomain misfolding.

Fujioka et al. show that, under starvation, yeast Atg1 forms droplets that concentrate autophagy factors, boosting Atg8 lipidation and clustering vesicles. These droplets likely serve as hubs that generate membrane seeds for autophagosome formation.

Liu et al. show that SPIN90 dimerizes and binds two Arp2/3 complexes to nucleate two bidirectional actin filaments and the dimerization domain is conserved in multicellular animals, suggesting that the mechanism of bidirectional actin filament nucleation is conserved.

Vega-Gutiérrez et al. present cryo-electron microscopy structures of GluA4-containing AMPA receptors, which are key for brain signaling. They show GluA4-specific conformations and explain how subunit composition shapes receptor architecture, dynamics and function.

Francis et al. used cryo-electron microscopy to show how a SPIN90 dimer activates the metazoan Arp2/3 complex to nucleate linear actin filaments for unidirectional and bidirectional growth, forming potential scaffolds for rapid assembly of dynamic actin networks.

The authors develop a computational method to design small DNA-binding proteins (DBPs) that target specific sequences. Designed DBPs show structural accuracy and function in both bacterial and mammalian cells for transcriptional regulation.

Wei et al. show that the primary function of m⁶A on the nuclear long noncoding RNA Xist, a master regulator of X inactivation, is to promote RNA degradation. Xist turnover is mediated by the nuclear exosome targeting complex and occurs independently of the nuclear m⁶A reader YTHDC1.

Here, the authors solve a series of cryo-electron microscopy structures that show how transfer RNAs (tRNAs) can guide the assembly of the multisubunit poxvirus RNA polymerase, uncovering a role of tRNA as an assembly chaperone.

Using a transposon-based approach to create a set of large genomic rearrangements, Dauban et al. demonstrate that interactions of lamina-associated domains with the nuclear lamina involve multiple contacts of varying strength.

Yang et al. uncover the molecular details of how mitochondrial proteins cross the outer and inner mitochondrial membranes, with hydrophobicity guiding them into distinct pathways toward specific destinations.

IST2 serves as a tether between the endoplasmic reticulum and the plasma membrane in yeast. Here, Arndt et al. interrogate its interaction with OSH6, revealing that the two proteins remain associated during lipid shuttling.

Reddy et al. used ancestral protein reconstruction, cryo-electron microscopy and functional assays to elucidate how a secondary active transporter evolved to harness the energy of sodium gradients to power the concentrative uptake of its substrate.

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.