Research articles

The authors present the full-length dimeric TRIM72 E3 ubiquitin ligase and the architecture of its high-order assembly bound to a phosphatidylserine-enriched membrane, providing insights into its role in membrane repair and ubiquitylation.

This study describes an approach to segment and extract key biophysical parameters from live-cell three-dimensional single-molecule imaging trajectories. The authors use this approach to study how NuRD assembles on chromatin and how it regulates enhancer dynamics.

Here, the authors constructed a deep-learning approach to design closed repeat proteins with central binding pockets—a step towards designing proteins to specifically bind small molecules.

The authors solved the cryo-EM structure of Myomaker, essential for myoblast fusion, and showed that it adopts a GPCR-like fold. They pinpointed the role of the dimeric interface and lipid-binding sites for fusion, and proposed a mechanism that may be conserved between species.

Release of inorganic phosphate (P_i) from actin marks older actin filaments for disassembly. Here, the authors show how P_i exits the F-actin interior through a ‘molecular backdoor’. The backdoor arrangement is distorted in a disease-linked actin variant.

Here, the authors show that PDHE1α accumulates at DNA double-strand breaks, in a PARylation-dependent manner, where it locally supplies acetyl-CoA for histone acetylation. These events facilitate remodeling of the chromatin landscape and efficient repair.

Here, using cryogenic electron microscopy and cryoDRGN, the authors delineate how the anaphase-promoting complex/cyclosome is reconfigurated to interact with its cognate E2s and thus polyubiquitinate its target. Unexpectedly, multiple ubiquitin moieties are shown to interact with the anaphase-promoting complex/cyclosome machinery, including its activator Cdh1.

Here, the authors unveil the intrinsic ability of the C terminus of SSX, as part of different oncogenic fusions, to determine fusion occupancy independent of the BAF complex by both recognizing and stimulating histone H2AK119 monoubiquitylation by PRC1.1.

Here the authors show that the m⁶A modification on mRNAs mediates their length-dependent enrichment in stress granules, and that mRNAs with longer exons—which usually harbor more m⁶A sites—are preferentially enriched in the granules.

By obtaining structural snapshots of the catalytic cycle of NADH:quinone oxidoreductase from Vibrio cholerae, the authors uncover its mechanism. They show how electrons are shuttled and determine the importance of the [2Fe-2S] cluster in the movement of the electron transfer switch.

Here, using cryo-EM, the authors show how Cas1–Cas2/3 and integration host factor, by means of a U-shaped bend that traps the invading DNA and a loop that positions it for the integrase, regulate integration of foreign DNA into the first repeat of the CRISPR array.

Here, the authors show that DYNLL1 accumulates at DNA double-strand breaks via 53BP1, where it inhibits MRE11-dependent end resection by disrupting its dimerization, and it restricts recruitment of the Shieldin complex.

Here authors present SAMOSA-ChAAT, a method for resolving how chromatin-interacting proteins restructure individual chromatin fibers, in high throughput and at scale. They provide evidence that the imitation switch family remodeling enzymes sense nucleosome density to program internucleosomal spacing on individual molecules.

Here the authors report structural and biochemical analyses of the mitochondrial TOM–TIM23 supercomplex, providing insights into how the substrates are transported through the outer and inner membranes.

Goekbuget et al. characterize the role of the developmentally essential transcriptional repressor FOXD3 in limiting transcription of highly active genes upon entry into S phase to promote faithful DNA replication and to protect genome integrity.

Mitochondrial DNA is critical for cell function, but how growing cells maintain stable concentrations is unclear. Seel et al. find that cells couple mitochondrial DNA copy number directly to cell volume through nuclear-encoded limiting factors, whose amount increases with cell volume.

Here the authors develop CRISPR–ChIP to enable the identification of factors required for chromatin regulation. Using this new method, they unveil a functional partitioning of H3K79 methylation into two distinct regulatory units, with important implications in MLL leukemia.

Capper et al. uncover how bicarbonate binds to the anion exchanger 1 (AE1), elucidate how drugs inhibit AE1 via distinct mechanisms, and generate a series of AE1 inhibitors using structure-based drug discovery.

A family of large-genome bacteriophages assembles a protective protein shell around its replicating DNA called the ‘phage nucleus’. Here, Enustun et al. use proteomics to identify a set of proteins associated with the phage nucleus that aid macromolecule transport through the nuclear shell.

The proteasome core particle (CP) assembles through the fusion of two half-CP precursors, yielding a complete but immature CP structure. Here the authors identify by cryogenic electron microscopy the structure of a post-fusion assembly intermediate, revealing how associated factors collaborate to chaperone CP assembly and maturation.