Table of Contents Alert: The FEBS Journal, Vol. 293, No. 10, May 2026
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The FEBS Journal Volume 293, Issue 10 Pages: 2795-3091 May 2026
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Issue Information
Free AccessIssue Information
Pages: 2795-2798 | First Published: 20 May 2026
Cover Illustration
AlphaFold3- predicted tertiary strucrures of fungal metallocarboxy-peptidase family. Visualised with Pymol. Image courtesy of Peter Lyons and colleagues, authors of the Original article included in this issue, pages 2928–2950.
Viewpoint
Linking RNA methylation to structure: a biophysical perspective
Pages: 2799-2810 | First Published: 08 January 2026
RNA methylation influences RNA structure and function, yet current detection methods are often complex or indirect. Biophysical approaches offer a powerful alternative, enabling direct and label-free analysis of RNA molecules. Here, we emphasize FT-IR spectroscopy for detecting global RNA methylation levels, and circular dichroism spectroscopy for analyzing RNA conformations. These techniques provide a powerful and accessible framework to explore RNA methylation from a structural and analytical perspective.
Structural Snapshot
Bridging the gap: When transcription meets translation
Pages: 2811-2820 | First Published: 10 January 2026
Gene expression comprises mRNA transcription from DNA by RNA polymerase, and translation to protein by the ribosome. Bacterial RNA polymerase cooperates with the ribosome in a supramolecular assembly line, which provides new functions. Recently, formation of this complex was visualized, providing insights into mRNA recruitment. RNA polymerase delivers nascent mRNA either directly or via ribosomal protein bS1, which captures and guides mRNA for proper positioning and initiation of translation.
Commentary
Open AccessTargeting the Notch receptor dimerization domain to inhibit Notch signalling—A new avenue of therapeutics
Pages: 2821-2824 | First Published: 28 January 2026
Notch signalling is an evolutionarily conserved signalling pathway that directs cell growth and differentiation across multiple tissue types, and its regulation must be controlled across the lifespan. Aberrant Notch signalling due to genetic mutations that occur within the negative regulatory region of the Notch 1 gene is linked to the development of acute T-cell leukaemia in humans. Liu et al. developed a range of novel peptide inhibitors that target the heterodimerization domain within the negative regulatory region of the Notch receptor. Here, the possible biological and therapeutic consequences are discussed.
Comment on: https://doi.org/10.1111/febs.70312.
Original Article
Open AccessDimerization‐dependent NOTCH receptor transactivation unveils a class of highly selective NOTCH signalling inhibitors
Pages: 2825-2844 | First Published: 01 November 2025
NOTCH signalling is indispensable for tissue homeostasis and, consequently, corruption of its normal function promotes numerous diseases, including cancer. However, the development of targeted therapies has been hampered by inefficacy and overt toxicity. Here, we show that NOTCH receptor dimerization is necessary for receptor transactivation, which has enabled the discovery of a previously unknown class of highly selective NOTCH signalling inhibitors that could underpin novel therapeutic approaches to treating NOTCH-driven pathologies.
Open AccessLimited roles of the miR‐17‐92 cluster in the regulation of T‐cell apoptosis
Pages: 2845-2861 | First Published: 06 January 2026
The pro-apoptotic protein BIM shapes T-cell survival and function, but how it is regulated remains unclear. In a mouse model lacking direct miR-17-92:Bim interactions, we observed a moderate reduction in Th17 CD4+ T cells. BIM levels were modestly increased in double-positive thymocytes and naive CD8+ T cells, but this did not affect overall T-cell development or homeostasis. Our findings point to alternative pathways controlling BIM-driven apoptosis in T cells. Created with BioRender.com.
Targeting the histone‐fold dimerization interface of oocyst rupture proteins from Plasmodium berghei for antimalarial inhibitor discovery
Pages: 2862-2884 | First Published: 08 January 2026
A physical interaction between two oocyst rupture proteins (ORP1 and ORP2), from the oocyst stage of the Plasmodium parasite that causes Malaria, has been shown to induce oocyst rupture. Rupture occurs in the salivary glands of the mosquito vector host and represents a key event in parasite transmission to humans. We reveal how these proteins interact at a molecular level, and we identify six cyclic peptides as potential oocyst rupture blocking molecules.
Open AccessCharacterisation of a phylogenetically distinct PL25 family ulvan lyase from a seaweed biomass enriched metagenome
Pages: 2885-2907 | First Published: 21 January 2026
Ulvan is a polysaccharide available from green seaweed with beneficial properties for various applications. The full potential of ulvan requires enzymatic degradation of the polymer, thus producing ulvan oligosaccharides. This study expands the armoury of characterised ulvan lyases. The characterised PL25 ulvan lyase, identified from a seaweed biomass metagenome enriched in an intertidal coastal hot spring, has distinct features that ensure efficient ulvan enzymatic treatment into tetrasaccharides and disaccharides.
Open AccessPhycocyanobilin biosynthesis in Galdieria sulphuraria requires isomerization of phycoerythrobilin synthesized by bilin reductases
Pages: 2908-2927 | First Published: 10 January 2026
The biosynthesis of bilins, tetrapyrroles essential for light harvesting and sensing, is performed by specific enzymes (FDBRs). In Galdieria sulphuraria, both phycobiliprotein types bind phycocyanobilin, despite lacking the canonical synthesizing gene PCYA. Instead, PEBA and PEBB are encoded, producing phycoerythrobilin, proposed to be later isomerized to phycocyanobilin. Phylogenetic and enzymatic analyses presented in this work confirm this unique biosynthetic route, highlighting a unique evolutionary diversification of pigment biosynthesis in Rhodophytes.
Editor's Choice
A novel glutathione transferase harboring an FMN redox cofactor
Pages: 2928-2950 | First Published: 12 January 2026
Glutathione transferases (GSTs) are a widespread superfamily of multifunctional enzymes with key roles in detoxification and secondary metabolism. Our study reveals that the little-known Iota-class GSTs (GSTIs) are mainly found in lower photosynthetic organisms and in a few fungi. Investigating SynGSTI1 from the model cyanobacterium Synechocystis, we discovered its unique structure, flavin cofactor binding, and roles in redox balance and stress tolerance. These findings establish GSTIs as a distinct GST subclass with important functions in redox homeostasis and stress tolerance, which are critical to photosynthetic life.
In vitro affinity maturation of a single‐chain antibody against thyroxine based on computer‐aided design
Pages: 2951-2968 | First Published: 14 January 2026
Thyroxine (T4) plays a critical role in regulating various physiological functions in the human body. Here, we aimed to achieve in vitro affinity maturation of T4-specific single-chain variable fragments through computational design, identify variants with enhanced affinity, and elucidate their interaction mechanisms with T4.
Deubiquitinase inhibitors: Targeting SARS‐CoV‐2 papain‐like protease with antiviral efficacy in a murine model
Pages: 2969-2998 | First Published: 12 January 2026
SARS-CoV-2 PLpro is a viral protease crucial for viral replication and immune evasion and is structurally and functionally similar to cellular deubiquitinating enzymes (DUBs). Utilizing this resemblance to DUBs, we identified antivirals with potent in vitro and in vivo efficacy against SARS-CoV-2. Additionally, using a combination of X-ray crystallographic and biochemical analyses, we uncovered the molecular mechanisms of PLpro inhibition, providing insights for the rational design of next-generation inhibitors.
Mitochondrial uncoupler BAM15 ameliorates liver lipid metabolism disorders by activating the AMPK pathway
Pages: 2999-3014 | First Published: 12 January 2026
Mice were fed a high-fat diet, and an in vitro cellular high-fat model was established. The mitochondrial uncoupler BAM15 mediates mitochondrial autophagy by activating the AMPK pathway in both liver and AML12 cells, thereby regulating mitochondrial quality control to alleviate lipid metabolism disorders in the liver induced by the high-fat diet.
Capillary differences with age and muscle fiber type are attenuated by accounting for fiber shape
Pages: 3015-3025 | First Published: 10 January 2026
Accounting for myofiber shape reduces apparent age-related declines in muscle capillarization by ~10–25% and fiber type differences by ~25–45%. Shape-sensitive metrics may prevent overestimation of capillary loss and improve interpretation of interventions targeting muscle vascular health.
Rickettsia parkeri subverts nicotinamide adenine dinucleotide (NAD+) metabolic pathway for its survival in endothelial cells
Pages: 3026-3041 | First Published: 28 January 2026
Rickettsia parkeri rickettsiosis is a tick-borne human disease. In humans, R. parkeri primarily infects endothelial cells. In this study, we noted that R. parkeri infection modulates nicotinamide adenine dinucleotide (NAD+) pathway for its survival in these cells. Studies like these would not only provide information on how R. parkeri interacts with host cells but also could lead to the development of strategies to target this and perhaps other rickettsial pathogens.
Structural insights into promoter recognition by Aca7
Pages: 3042-3049 | First Published: 16 January 2026
Aca7 from Halomonas caseinilytica functions as a transcriptional regulator by recognizing an inverted repeat in the AcrIF11-Aca7 operon promoter. Dimeric Aca7 binds double-stranded DNA through major groove interactions and stabilizes DNA bending via minor groove contacts. Structural analysis of the Aca7-DNA complex provides mechanistic insight into promoter recognition.
A perilysosomal feedforward mechanism regulates starvation‐induced calcium signaling
Pages: 3050-3074 | First Published: 16 January 2026
Cells respond to nutrient starvation by initially releasing lysosomal Ca2+ through TRPML1. This causes depletion of endoplasmic reticulum (ER) Ca2+ and activation of store-operated Ca2+ entry via ER-lysosome Ca2+ shuttling. The resulting increase in perilysosomal Ca2+ promotes a feedforward mechanism through direct binding of Ca2+-bound calmodulin to TRPML1, which potentiates the entire sequence of events. Ca2+-bound calmodulin also regulates the magnitude of the starvation-induced Ca2+ signal by controlling the rate of Ca2+ extrusion.
Surface loops may provide additional function necessary for enzyme‐to‐pseudoenzyme transition in the fungal metallocarboxypeptidase family
Pages: 3075-3091 | First Published: 14 January 2026
Some proteins look like enzymes but lack enzymatic function; these pseudoenzymes are thought to arise following a gene duplication event. What allows for their selection in the absence of enzymatic function? Our study of fungal metallocarboxypeptidases suggests that the acquisition of surface loops can provide function, in the form of new protein-protein interactions, necessary for selection. We explore this through bioinformatics, modeling, and biochemical analyses.
