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The distinct architecture of the Escherichia coli membrane transporter LetA mediates lipid trafficking across the bacterial envelope in partnership with the tunnel-like complex LetB.

Phosphorylation-dephosphorylation and ubiquitination tune TCR signaling to avoid self-reactivity. Kim and colleagues show that acetylation also modulates TCR signaling.

This study provides new insights into the role of endoglin (ENG) as a co-receptor in endothelial cells and addresses a gap-in-knowledge on how ENG could be involved in both TGF-β and BMP9 signalling. Such knowledge greatly facilitates therapeutic targeting of ENG-related pathways.

Rapid immune activation requires tight control of mRNA stability in CD8⁺ T cells. Here, the authors show that a compositive RNA motif – m⁶A sites positioned next to AU-rich elements - marks mRNAs for rapid decay during activation, revealing a coordinated mechanism that shapes T-cell immunity.

A technique called condense-seq has been developed to measure nucleosome condensability and used to show that mononucleosomes contain sufficient information to condense into large-scale compartments without requiring any external factors.

Taveneau et al. leverage artificial-intelligence-driven protein design to create inhibitors that control RNA-targeting enzymes in cells, revealing a strategy to rapidly design off-switches for RNA-editing systems.

Lactate fuels cancer growth by activating ERK signaling through GCN5-mediated lactylation of ERK, which disrupts ERK–MEK interactions. Development of a cell-penetrating peptide blocking lactylation slows KRAS-mutant tumor development.

Epstein–Barr virus (EBV) is a widespread herpesvirus linked to cancer and autoimmune disease. The authors in this work design and characterize a stabilized prefusion form of gB, an essential viral fusion protein, advancing EBV vaccine and therapeutic development.

Reovirus mRNAs lack polyadenylated tails yet are efficiently translated. Here, the authors identify host protein ataxin-2-like (ATXN2L) as a mediator of reovirus nonpolyadenylated mRNA translation.

Vassy, Dornisch and colleagues developed a genomics-based prostate cancer risk model to support a randomized clinical trial of precision screening in a national healthcare system.

A combination of biochemical, cell biological and electron microscopy analyses reveal a ‘nucleotide code’ that coordinates Lis1–dynein binding stoichiometry, which in turn governs Lis1’s ability to relieve dynein autoinhibition.

Polyamines prevent the action of kinases on acidic phosphorylatable motifs in spliceosomal proteins, thus providing a mechanism for metabolite-mediated regulation of alternative splicing in cells.

Cullin-RING ligases are regulated by the COP9 signalosome (CSN) through deneddylation. Here, authors report high-resolution cryo-EM structures that capture catalytic and dissociation intermediates, identify CSNAP within the complex, and reveal a stepwise pathway for CSN disengagement.

Using activity-based chemical probes, oncogenic IDH1-R132H but not the wild type was found to acquire a unique autopalmitoylation at C269. This mutant-specific modification is critical for the enzyme’s abnormal activity in cancer.

Large-scale computational and in vitro analyses identify commensal type III secretion systems and substrates in the human gut microbiome that can interact with human proteins to modulate immune pathways.

Viral ribonucleoprotein–viral protein networks form pre-replication centres that nucleate viral factories and drive respiratory syncytial virus replication.

In targeted protein degradation, a degrader molecule brings a neosubstrate protein proximal to a hijacked E3 ligase for its ubiquitination. Here, pseudo-natural products derived from (−)-myrtanol—iDegs—are identified to inhibit and induce degradation of the immunomodulatory enzyme indoleamine-2,3-dioxygenase 1 (IDO1) by a distinct mechanism. iDegs prime apo-IDO1 ubiquitination and subsequent degradation using its native proteolytic pathway.

Heparan sulfate proteoglycans facilitate the assembly of clusters of glycoRNAs and cell surface RNA-binding proteins, which negatively modulate VEGF-A signalling and angiogenesis.

Circulating N-glycomics studies have shown alterations in multiple cancer types. Here, the authors show that blood-based glycome patterns on proteins can be used to predict liver damage and liver cancer development.

Targeting neurons that regulate energy balance may offer new approaches for obesity treatment. Here, authors show that chemogenetic and pharmacological manipulation of GABAergic neurons in the DRN/vlPAG increases adaptive thermogenesis and reduces weight gain in mice fed a highfat diet.

A look back through 150 years of Nature front page designs.

Here, the authors report recent updates to the ENCODE data portal including a redesigned home page, an improved search interface, custom-designed pages highlighting biologically related datasets and an enhanced cart interface for data visualisation plus user-friendly data download options.

Lipid phosphate phosphatases (LPPs) catalyze the dephosphorylation of bioactive lipid phosphates. In this study, the authors employ structural and biochemical investigations on human LPP1, elucidating its catalytic mechanism and suggesting a potential regulatory role for PIP₂.

PCNA–PAF15 has a key role in determining replisome dynamics during genome replication and protecting against genome instability.

Hexokinase detachment from the outer mitochondrial membrane is shown to support aerobic glycolysis in cancer cells. Differential localization of the HK1 isoform to the outer mitochondrial membrane, compared to the HK2 isoform, explains the conditional essentiality of HK2 in cancer cells cultured in physiologic media.

Using a mouse model with a macrophage-specific DNA repair defect, Niotis, Arvanitaki et al. identify DNA damage-induced autophagy in macrophages as a link from aging to autoimmunity.

This study provides structural insight into the dynamic catalytic mechanism of OsSPS3, a key enzyme in plastoquinone-9 biosynthesis. OsFBN5 enhances the activity of the OsSPS3 dimer by shifting its catalytic mechanism from alternating to synchronous.

A rationally designed assay detects granzyme A activity by integrating peptide-based GzmA-targeted inhibitors and probes with chemiluminescent reporters to monitor inflammatory bowel disease.

NatD is an acetyltransferase responsible for N-α-terminal acetylation of the histone H4 and H2A and has been linked to cell growth. Here the authors show that NatD-mediated acetylation of histone H4 serine 1 competes with the phosphorylation by CK2α at the same residue thus leading to the upregulation of Slug and tumor progression.

Chen et al. show that PEX39 cooperates with PEX7 in the peroxisomal import of proteins containing a PTS2 site and uncover an (R/K)PWE motif in PEX39 and PEX13 that binds to PEX7 and facilitates the import of PTS2-containing proteins.

A histone ubiquitin-dependent regulatory hub governs stimulus-dependent heterochromatin propagation, with important implications for understanding mechanisms governing rapid changes in the epigenetic landscape in physiology and disease.

Patients with myelodysplastic syndromes (MDS) have limited therapeutic options. Here the authors show that functionally impaired NK cells contribute to immune escape of pre-malignant clones in early stage MDS and that NK adoptive cell therapy can be considered to prevent or delay the development of MDS.

S protein interacts with and activates PBP1a during cell division, as part of a larger GpsB-associated multiprotein complex that coordinates peptidoglycan remodelling in Streptococcus pneumoniae.

Chaperone-mediated autophagy (CMA) is often dysregulated in cancer, but its mechanisms remain unclear. This study reveals that MST4- mediated LAMP2A phosphorylation regulates CMA by stabilizing lysosomal LAMP2A, thereby promoting GBM tumorigenicity and immune evasion.

Zhang et al. found that histone deacetylase 1 (HDAC1) condensation is responsible for temozolomide resistance in glioblastoma by recruiting CCCTC-binding factor and remodeling chromatin in a deacetylase-independent manner. Disrupting the HDAC1 condensates with resminostat restores the sensitivity to temozolomide.

Stanage et al. identify a role for transfer RNA nuclease SLFN11 in replication-stress-induced cell death in cisplatin-treated cells lacking PrimPol. SLFN11 is activated upon single-stranded DNA accumulation at stalled forks followed by replication protein A exhaustion and cell death.

Qian and colleagues show that IL-17REL functions as a decoy receptor to suppress the effects of IL-17 family cytokines and reduce intestinal inflammation.

Zhuang, Zi et al. identify cyclin-dependent kinase 3 (CDK3) as a driver of neuron loss in Alzheimer’s disease that is associated with brain atrophy and memory decline in mice. Inhibition of CDK3 (BMX330) is shown to limit neuronal loss and improve cognition.

Staphylococcus aureus can aggregate within human synovial fluid and lead to joint infections. Here, the authors reveal that the fatty acid kinase system and its downstream saeRS regulator control S. aureus aggregation within synovial fluid.

Bohlen and colleagues report that the E3 ubiquitin ligase CBL is necessary for the development, tolerance and activation of B cells in humans, unlike in mice where CBL deficiency results in loss of T cells.

Despite extensive structural studies elucidating how antigens are anchored to antigen-presenting molecules and presented to T cells, little is known about the display mechanism of the lipid-antigen-presenting molecule CD1c. Here, by combining structural immunology, lipidomics, and biophysical analysis, the authors reveal that the CD1c binding cleft accommodates two different lipids, one of them with a bulky headgroup positioned sideways for display to T cells, rather than upwards, different from the conventional upright antigen-presentation mode

Polygenic risk scores can help identify individuals at higher risk of type 2 diabetes. Here, the authors characterise a multi-ancestry score across nearly 900,000 people, showing that its predictive value depends on demographic and clinical context and extends to related traits and complications.

Using cryo-EM, the authors identified 42 MIPs, including outer junction protein CFAP77 and outer dense fibers, in native doublet microtubules of Tetrahymena thermophila. Knockout of CFAP77 reduced ciliary beat frequency and led to outer junction damage.

Multidrug efflux pumps help bacteria survive stress and promote antibiotic resistance. Here, authors define the molecular detail of an anaerobic-connected pump MdtF uncovering acid-responsive activity which may enable toxin control in certain niches.

A short peptide derived from a commensal-fungal-secreted protein promotes repair in models of colon epithelial damage when delivered directly or via probiotic microbes.

Zygnematophycean algae are the closest algal relatives of land plants. This study compares the osmatic stress response of two of these species, finding a core set of molecular protective components and providing insights into the toolkit needed for plant terrestrialization.

Installing algal pyrenoids or cyanobacterial carboxysomes into plants to enhance photosynthetic efficiency remains a formidable challenge. Here, the authors report the construction of CO₂-fixing nanocompartments by encapsulating Rubisco using encapsulin from Quasibacillus thermotolerans.

Cancer immunotherapy benefits from antibody-lectin chimeras that block glyco-immune checkpoints.