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AcrIF25 inhibits the type I-F CRISPR–Cas system by disassembling its ribonucleoprotein effector complex without an external energy source.

17β-oestradiol establishes an anti-ferroptotic state in female kidney tubules.

Bacteria evolving within humans employ strategies to overcome trade-offs. Here, the authors report that the cystic fibrosis-associated pathogen Burkholderia dolosa alternates phenotypes in vivo by accumulating successive de novo mutations.

Bacterial cell division depends on the dynamic assembly of FtsZ proteins, forming the Z-ring. Here, the authors show that the N-terminal intrinsically disordered region of FtsZ functions as a cis-acting disassembly element and is essential for Z-ring condensation at midcell in E. coli cells.

This study identifies TriDTCs as a family of terpene cyclases responsible for harzianol I and wickerol A biosynthesis in Trichoderma fungi and are found to regulate Trichoderma’s chlamydospore and Aspergillus oryzae’s sclerotia formation through producing harzianol I.

Our understanding of how post-translational modification—protein phosphorylation—impacts the complexity of eukaryotic signalling pathways is continuously expanding. Now, protein oligophosphorylation has been characterized as an additional phosphorylation mode. Structural and mass spectrometry methods revealed that NME1 catalysed its own oligophosphorylation, leading to altered protein–protein interactions.

The receptor-like kinase NIK1 is phosphorylated in response to multiple biotic and abiotic signals, activating the NIK1/RPL10/LIMYB signaling circuit, which coordinately regulates translation and photosynthesis in response to environmental changes.

The safety and efficacy of ribonucleoproteins for genome editing can be enhanced by formulations of lipid nanoparticles optimized for enhanced stability, delivery efficiency and editing potency of the protein complexes.

Human chromatin remodeller SMARCAD1 exhibits a substrate preference for subnucleosomal particles over the canonical nucleosome.

Long-circulating, transfection-competent LNP-mRNA systems are key for effective extrahepatic delivery. Here, authors show that LNPs with high bilayer lipid ratios yield high mRNA encapsulation, prolonged circulation, and enhanced transfection in extrahepatic tissues.

Here, the authors show that the oral microbe Streptococcus mutans, elevated in the gut microbiome of Parkinson’s patients, produces imidazole propionate via UrdA that in mice reaches the brain and triggers Parkinson’s-like pathology, suggesting a causal gut–brain axis disease link.

Das et al. show that the correct editing activity of the methionyl tRNA synthetase, regulated by AIMP3, is required to prevent the accumulation of homocysteine and the resulting cardiomyocyte cell death and cardiac dysfunction.

An RNA codon-expansion strategy enables incorporation of non-canonical amino acids into proteins of interest orthogonally to existing methods by inserting pseudouridine codons into specific mRNA transcripts and using an engineered decoder tRNA.

This study reveals that an outer membrane protein from the predator Bdellovibrio bacteriovorus forms a pentameric assembly that traps a lipid monolayer within. This allows the discovery of two superfamilies, distributed across a wide range of bacteria, likely to adopt a similar architecture.

A highly potent and selective small-molecule catalytic inhibitor of the protein lysine methyltransferase NSD2 shows therapeutic efficacy in preclinical models of KRAS-driven pancreatic cancer and lung cancer.

The molecular mechanism between each progesterone receptor (PR) isoform and oncogenic co-regulators SRC3 and p300 is poorly understood. Here, the authors report PR isoform-specific interactions with these co-regulators and antagonist-driven protein interactions, challenging the classical model of nuclear receptor activation.

The DNA breaks that initiate recombination during meiosis are resected by nucleases, but the mechanism of this resection in mammals is poorly understood. Here, the authors examine the roles of the MRE11-RAD50- NBS1 complex in beginning and extending resection during meiosis in male mice.

In plants, Rubisco is composed of 16 subunits and requires multiple chaperones to assemble. Features of individual tobacco Rubisco subunits that affect kinetic properties are investigated by coexpression with chaperones in Escherichia coli.

Monomethylation of histone H4 lysine 20 (H4K20me1) contributes to DNA replication but the mechanism is not well understood. Here, the authors identify a conserved tandem Tudor domain of BAHCC1 as a H4K20me1-specific reader, which promotes the recruitment of MCM complex to chromatin for efficient DNA replication.

Alfajaro et al identify that a bat MERS-like coronavirus HKU5 uses ACE2 as a receptor from its natural bat reservoir Pipistrellus abramus and American mink. Structural analyses demonstrate a unique interaction between the HKU5 receptor binding domain and bat ACE2. This highlights the receptor flexibility of merbecoviruses and identifies mink as potential intermediate hosts, informing viral surveillance and countermeasure development.

Species differences in innate immune sensing could impact nanomedicine development. Here the authors examine phagocyte recognition and show the defined molecular patterns on polymer-coated nanoparticles in different species are driven by ficolin and complement opsonisation.

Molecular glues have great potential for drug discovery if they can be systematically discovered. Konstantinidou, et al describe a scaffold-hopping approach using multicomponent reaction chemistry to design molecular glues that induce 14-3- 3σ/ERα formation in cells.

Mobilization of immature neutrophils (imNeu) can migrate from bone marrow (BM) to circulation and inflamed tissues. However, the mechanism of its mobilization and function remains unknown. Here the authors identify ILC1 mediates IL-10 producing imNeu mobilization to inflamed tissue via IFN-γ, thus tempering the acute inflammation.

Kinesin-1 utilizes ATP-driven conformational changes to transport vital intracellular cargoes along microtubules. The authors use cryo-EM to reveal a missing structural transition state of the kinesin-1 motor domain during ADP release that is unaffected by its autoinhibitory tail.

Licensing of eukaryotic origins of replication with MCM double hexamers (DHs) can occur through distinct pathways. Here, Lim et al. show that in yeast, cell cycle-dependent regulation of DH formation by CDK and origin structure have co-evolved.

Here, the authors identify and characterize three gut bacterial enzyme families that metabolize endogenous and synthetic steroid hormones, showing to act on diverse substrates, to exhibit gene fusions, and gender-linked prevalence, opening avenues for studying mechanisms of microbial-mediated steroid metabolism and host hormonal physiology.

Agreement forged in Paris aims to hold warming ‘well below’ 2 °C.

The authors integrate artificial intelligence with laboratory automation to create a widely applicable autonomous platform for efficient and scalable enzyme engineering.

UM171 promotes corepressor degradation by acting as a molecular glue to induce KBTBD4–HDAC1/2 interactions with the help of inositol hexakisphosphate.

Rashan, Bartlett and colleagues show that mammalian 4-hydroxy fatty acids are primarily catabolized by ACAD10 and ACAD11 (atypical mitochondrial and peroxisomal acyl-CoA dehydrogenases, respectively) that use phosphorylation in their reaction mechanisms.

PRS-CSx is a polygenic risk score construction method that improves cross-population polygenic prediction by integrating GWAS summary statistics from multiple populations.

The management of ulcerative colitis (UC) remains challenging due to the complexity of its etiology. Here, the authors establish that argininosuccinate synthetase 1 (ASS1) and its metabolite arginine are pivotal inducers of UC, through the triggering of mTOR and iNOS activation, and the induction of gut microbiota dysbiosis by metabolomics and proteomics. Inhibition of ASS1 by C-01 provides a viable strategy for the treatment of UC.

Chimeric antigen receptor (CAR)-T cell is a promising therapy for hematological malignancy, but further optimization is still desirable. Here the authors show that incorporating CD99, a membrane protein expressed on activated T cells, transmembrane and juxtamembrane domains into CAR design helps improve CAR-T efficacy in vitro and in vivo in mice.

Bats harbor diverse viruses but it’s less clear how they tolerate infection. Here, by characterizing innate immune responses in bat cells the authors show that IFN-beta signaling resists antagonistic activity by viruses and identify interferon stimulated genes with enhanced antiviral activity.

Scientists find that spongin, a key biomaterial in sponges, contains the same collagens as mammals and that these biocomposites contain brominated crosslinks. Now, the question: “Maybe we are all sponge to some degree?” is no longer so absurd.

LaccID, an engineered laccase, enables hydrogen-peroxide-free proximity labeling and electron microscopy (EM) in mammalian cells. Notably, LaccID is selectively active at the cell surface, enabling the mapping of the dynamic T cell–tumor surfaceome and its use as a genetically encodable EM tag, expanding the toolkit for cell-based imaging and proteomics.

DNA double strand break repair pathways ensure genome stability and prevent disease. Here the authors show that the actin nucleating factor DIAPH1 and γ-actin promote homologous recombination (HR)-dependent repair. Inherited mutations in DIAPH1 or ACTG1 give rise to clinical deficits similar to those associated with defective HR.

The antiviral dsRNA sensor PKR is regulated by PACT. This paper shows how PACT prevents aberrant PKR activation by endogenous dsRNAs like Alu. PACT disrupts PKR’s dsRNA scanning without blocking its binding, resetting its activation threshold to tolerate cellular dsRNA and preserve homeostasis.

Epichaperomics allow the study of protein-protein interactions and their alterations, but probes have been limited to capturing HSP90 epichaperomes. Here, the authors introduce and validate a toolset of HSP70 epichaperome ligands, and use them in epichaperomics to identify a mechanism with which cancer cells can enhance the fitness of mitotic protein networks.

Li et al. characterize overlapping and divergent metabolic requirements of human and murine NK cells in response to activation, with a focus on serine metabolism

Here, Isaacs, Nieto and Zhang et al. discover a potent nanobody and engineer a dual-action antibody that targets two viral proteins, offering strong protection against Nipah and Hendra viruses while preventing viral escape, potentially contributing to future treatments.

The presynaptic protein Munc13 forms nanoclusters at synaptic release sites, but its internal organization is unclear. Here, the authors show that two distinct ordered Munc13 oligomers couple synaptic vesicle docking and SNARE assembly to regulate neurotransmission

How the necroptosis executioner, MLKL, converts to a killer form has been mysterious. Here, authors show RIPK3-mediated phosphorylation of human MLKL is the cue for pseudokinase domain dimerization before assembly of pro-necroptotic MLKL tetramers.