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Viruses represent a major threat to human health, while simultaneously exhibiting great potential in a wide range of applications, from virus-inspired devices to therapeutic delivery agents. Addressing virus-related questions from an interdisciplinary standpoint promises to open new avenues, both in the fight against viral diseases and in the exploitation of viral structures to advance technology. This has stimulated the development of 'physical virology', a growing research field gathering researchers from various scientific disciplines with a common interest in viruses. The FEBS|EMBO Lecture course on Physical Virology brought together top researchers working with viruses to inspire and further educate a new generation of transdisciplinary virus-oriented scientists and to cement the growing physical virology community.
K. Dey , S. M. Rahaman , T. Chakraborti , and S. Chakraborti , "Role of Phospholemman and the 70 kDa Inhibitor Protein in Regulating Na+/K+ ATPase Activity in Pulmonary Artery Smooth Muscle Cells under U46619 Stimulation," FEBS Letters 587, no. 21 (2013): 3535-3540. https://doi.org/10.1016/j.febslet.2013.09.011. The above article, published online on 18 September 2013 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Michael Brunner; the Federation of European Biochemical Societies; and John Wiley & Sons Ltd. A third party reported on PubPeer [1] that there was evidence of duplication of bands in Figure 1D and duplication and manipulation of image elements in Figure 4C. An investigation by the journal and publisher confirmed that Figures 1D and 4C had been manipulated. They also found evidence of duplication and manipulation between Figures 2A and 2B, as well as evidence of duplication between Figure 4B and the first three bands in Figure 5B. The authors did not initially respond to an inquiry about these concerns by the publisher. The retraction has been agreed to because the evidence of image manipulation within this article fundamentally compromises the editors' confidence in the results and conclusions as presented. The authors were informed of the retraction. References [1] Brachystigma wrightii. Comments on "Role of phospholemman and the 70 kDa inhibitor protein in regulating Na+/K+ ATPase activity in pulmonary artery smooth muscle cells under U46619 stimulation," PubPeer, March 2026. https://pubpeer.com/publications/1E450411C9E5FB2DC607F7D229B95A.
Q. Jiang , F. Li , K. Shi , P. Wu , J. An , Y. Yang and C. Xu , "ATF4 Activation by the p38MAPK-eIF4E Axis Mediates Apoptosis and Autophagy Induced by Selenite in Jurkat Cells," FEBS Letters 587, no. 15 (2013): 2420-2429, https://doi.org/10.1016/j.febslet.2013.06.011. The above article, published online on 19 June 2013 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors; the journal Editor-in-Chief, Michael Brunner; the Federation of European Biochemical Societies; and John Wiley & Sons Ltd. The retraction has been agreed upon following concerns raised by a third party. An investigation identified several instances in which elements appear to be duplicated across different figures, including between Figures 1B and 3F, 2C and 5F, 5F and 6A, and 3E and 5E. Additional duplications were identified within Figures 1C and 5B. Further duplications were observed involving elements from Figures 1A, 1C, 3E, and 6D of this article and figures published in a later article elsewhere by some of the same authors. The authors acknowledged some of the duplications and indicated that these arose during figure preparation. Due to the time that has elapsed since publication, the original data are no longer available. The editors consider the results and conclusions of this article to be unreliable. The authors did not respond to our notice of retraction.
Aminoacyl-tRNA synthetases (ARSs) are a family of enzymes that attach amino acids to tRNAs. To date, all 37 human ARS genes have been implicated in genetic diseases, affecting over a thousand patients worldwide. At the 2025 Federation of European Biochemical Societies (FEBS) Special Meeting 'Expanding Frontiers in Aminoacyl-tRNA Synthetase Research', patients, families, and advocacy groups communicated the need for a unified approach for reporting on ARS gene names and associated conditions in the scientific literature. This request stemmed from the current use of multiple nomenclature systems and the desire of these individuals to rapidly identify published data on specific ARS genes. Here, we summarize ARS gene nomenclature and request that the scientific community adhere to a single nomenclature system.
Biological aging is associated with gut microbiome alterations, including depletion of commensals and enrichment of disease-linked pathobionts. However, the extent to which these changes overlap with disease-associated microbiome signatures remains unclear. Here, we re-examined 45 454 gut microbiomes (141 studies) to quantify overlap between aging-associated microbiome alterations and six major diseases. Cardiometabolic diseases showed the greatest overlap, followed by colorectal cancer. We identified 15 microbes enriched with aging and depleted in health, of which > 50% belonged to oral-associated Streptococcus, Veillonella and Rothia clades. Review of two population-level cohorts (6029 subjects) revealed reproducible associations between these microbes and seven cardiometabolic disease-linked medications. We further discuss their medication associations and propose strategies to deconfound medication- and disease-associated microbiome signatures in aging studies.
MreC is an essential periplasmic component of the bacterial elongasome that regulates peptidoglycan synthesis through interaction with PBP2. Here, we report the crystal structure of MreC from Acinetobacter baumannii (abMreC) at 2.49 Å resolution. The structure reveals a conserved elongated fold composed of two β-barrel domains and exists as a monomer in solution. Structural comparison with homologs shows that while the overall architecture is conserved, surface-exposed regions involved in protein-protein interactions vary significantly. AlphaFold3-based modeling of the abMreC-abPBP2 complex, supported by mutational and pull-down assays, identifies key interface residues. Comparison with the Helicobacter pylori complex indicates that MreC employs a conserved binding mode while accommodating diverse interface architectures to regulate PBP2 activity.
The nucleocapsid (N) protein of SARS-CoV-2 is central to viral assembly and replication. It binds the viral RNA to form a helical nucleocapsid and enables genome packaging and its release into host cells. Human heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), one of the most abundant RNA-binding proteins in eukaryotes, regulates key aspects of RNA metabolism, including splicing, transcription, localisation, and transport. Here, we report a direct physical interaction between the SARS-CoV-2 N protein and hnRNPA1, primarily mediated through their intrinsically disordered regions. Furthermore, we found that these proteins co-phase separate in vitro and colocalise within stress granules in cells. In vivo studies reveal that hnRNPA1 suppresses viral replication, suggesting that the N protein-hnRNPA1 interaction plays an important role in modulating the viral life cycle.
DNA damage and replication stress cause genome instability. Histone H3/H4 deacetylation by class I histone deacetylases (HDACs) and H3 methylation by histone methyltransferases promote DNA repair and fork stability. However, other histone modifications and enzymes involved remain unclear. Here, in the fission yeast Schizosaccharomyces pombe, we found that histone H2B N-terminal K5, K10, and K15 residues were deacetylated by the class II HDAC Clr3 under DNA damage and replication stress. Clr3 or SHREC was recruited to DNA breaks and stressed forks by interacting with Rad9-Rad1-Hus1. H2B hyperacetylation and Clr3 loss disrupted chromatin compaction, impaired sister chromatid cohesion, suppressed Rad51 loading and homologous recombination, and exhibited genotoxic sensitivities. Our findings reveal a novel role for H2B deacetylation by class II HDACs in genome stability.
Inositol phosphates (IPs) and phosphoinositide lipids (PIPs) are regulatory molecules critical for a wide array of functions in eukaryotic cells. Membrane PIPs have clear functions in transient recruitment of signaling proteins to membranes, and IPs have been found locked in the core of proteins as structural cofactors. However, several recent studies have suggested IPs and PIPs can mediate protein-protein interactions at the interface between proteins, functioning as natural molecular glues. Here, we present recent structural biology describing how IPs and PIPs mediate these regulatory responses at protein interfaces. In addition, we describe protein-protein interactions mediated by IPs and PIPs, for which evidence supporting a natural molecular glue role is unclear or awaits further high-resolution structural analyses. Together, we put forth that PIPs and IPs have a historically under-appreciated role at protein-protein interfaces, requiring a more systematic, structural approach to elucidate.
The molecular mechanisms by which artificial electron mediators, such as ethyl viologen (EV), interact with tungsten-containing formate dehydrogenases (FDHs) during reversible CO2 reduction remain poorly understood. Here, we reveal an unexpected alternative mediator interaction site in FDH1 of Methylorubrum extorquens AM1. Removing the native flavin mononucleotide cofactor abolishes NAD+-dependent activity but preserves EV-driven catalysis. Through mutagenesis, kinetic analysis, and molecular docking, we identified a cooperative aromatic network-comprising residues F232, F471, and Y329-that stabilizes EV via stacking interactions near the proximal B1 iron-sulfur cluster. Disrupting these residues impairs EV-mediated electron transfer without destabilizing global structure. These findings reveal a dual interaction strategy for artificial mediators in tungsten FDHs, offering a structural framework to rationally engineer biocatalysts for CO2 conversion.
CT10 regulator of kinase (CRK) and CRK-Like (CRKL) are important Src homology 2 (SH2)- and SH3-domain containing signaling adaptors, which drive cell adhesion, motility, differentiation, and proliferation. Their genetically defined and overlapping roles include facilitating proper development of the vertebrate central nervous system. All four members of the SH2-domain containing (SH) protein family are enriched in YXXP motifs, which when the initial tyrosine is phosphorylated form the preferred binding motif of CRK family SH2 domains. We show that ABL kinase drives tyrosine phosphorylation of SH protein YXXP motifs and induces their direct binding to the SH2 domains of CRK family adaptors. The implications of the interactions between CRK/CRKL and SH proteins include signal attenuation and relocation of CRK adaptor signaling.
Altered glycosylation is a hallmark of cancer that shapes immune recognition within the tumor microenvironment. Lectins-glycan-binding proteins-play a dual role in this process: they interpret tumor-associated glycan patterns and can also be exploited as therapeutic tools. In this review, we discuss emerging strategies that harness lectins in cancer immunotherapy. Engineered lectin-based constructs, including antibody-lectin chimeras, lectin-drug conjugates, and glycan-targeting CAR-T cells, enable recognition of tumor-specific glycosylation signatures. At the same time, endogenous lectin pathways such as the galectin-polyLacNAc and sialic acid-Siglec axes function as glyco-immune checkpoints that suppress anti-tumor responses and represent promising therapeutic targets. Understanding how lectins regulate tumor-immune interactions may guide the development of next-generation immunotherapies integrating antigen recognition with glycan sensing.
The aberrant aggregation of α-synuclein (αS) into insoluble amyloid fibrils is a hallmark of Parkinson's disease. Despite recent advances in characterising the properties of mature αS fibrils, the transient and heterogeneous intermediates that underlie cellular toxicity remain largely elusive. Here, we review the mechanistic principles of αS aggregation, focussing on liquid-liquid phase separation (LLPS) as a critical intermediate step. We discuss how the structural evolution of αS within the condensed phase governs the subsequent patterns of cellular dysfunction and pathological propagation. This framework supports an emerging state-centric paradigm in therapeutic discovery, where the physical properties of αS condensates are modulated to mitigate the deleterious effects of its misfolding, offering a new sophisticated alternative to classical inhibition strategies.
Gram-negative bacteria produce nonulosonic acids, a family of nine-carbon sugars that mimic host sialic acids and may contribute to bacterial virulence. The nonulosonic acid C8-epimeric 5,7-di-N-acetyllegionaminic acid (8-epi-Leg5,7Ac2) is a component of the K-locus 49 (KL49) capsule of hypervirulent Acinetobacter baumannii, and its epimerization is proposed to be mediated by ElaA, ElaB, and ElaC. We identified a KL49 strain that induces lethal sepsis in mice and found deletion of elaA, elaB, or elaC abolished lethality and markedly reduced capsule production. Crystal structures of ElaB, ElaA, and ElaC revealed conserved N-acetyl recognition underlying CMP-Leg5,7Ac2 synthesis and regioselective C8 epimerization. Together, these genetic, structural, and in vivo findings identify ElaABC as potential antivirulence targets in emerging hypervirulent KL49 A. baumannii strains.
Mitochondrial oxidative phosphorylation relies on cytochrome c transferring electrons between complexes III and IV. Earlier studies using detergent-purified complex III-IV supercomplexes from S. cerevisiae showed that this transfer is limited by two-dimensional cytochrome c diffusion. This study investigates this process in membrane-embedded mitoplasts. The results show that membrane embedment shifts the rate-limiting step from cytochrome c-mediated electron transfer to the catalytic activity of the supercomplex itself. Up to a cytochrome c : supercomplex ratio of unity, turnover increases sharply regardless of ionic strength. At higher ratios, the rate levels out at 15-20 s-1, indicating that the process is no longer limited by salinity-dependent electron transfer, but rather by the catalytic capacity of complex IV.
Fluorescence recovery after photobleaching (FRAP) is a widely used technique for investigating protein dynamics in live cells. FRAP enables researchers to monitor protein mobility and binding interactions in real time, providing valuable insights into cellular regulatory mechanisms. Initially developed to explore membrane fluidity, FRAP has evolved to enable study of nuclear processes, including transcription factor (TF) dynamics crucial for gene regulation. In this review, we focus on how FRAP has advanced our understanding of TF dynamics in health and disease. TFs exhibit complex interactions with DNA that are essential for cellular function. FRAP helps to quantify these interactions, revealing how TF mobility and chromatin binding influence gene expression patterns. We further explore the role of FRAP in studying TFs in disease. Research on TF dynamics in cancer, diabetes, and osteoarthritis underscores the method's potential to identify disease-related regulatory mechanisms. By providing a nuanced understanding of TF behavior, FRAP presents a promising avenue for developing targeted therapies across diverse pathologies.
Embryo-like structures, or stembryos, complement embryo research in innovative ways and provide an alternative when embryo utilization is ethically or technically limited. These models, however, are hindered by experimental variability and limited developmental potential, whose causes are still not fully understood. Establishment of appropriate DNA methylation patterns is crucial for mammalian development but characterization of DNA methylation in stembryo models has been largely overlooked. This Perspective manuscript highlights this knowledge gap and suggests that characterization of DNA methylation, and in the future also of other epigenetic modifications, should become standard practice in stembryo model characterization. Available datasets indicate that differences in DNA methyltransferase expression between stembryos and embryos exist, thus suggesting an avenue of investigation to further improve these models.
Organisms utilize sophisticated neurocircuitry to select optimal food sources. Methylobacterium is a lifespan-promoting diet for C. elegans that drives faster development and longevity; however, after ingestion, C. elegans consistently choose any other food option available. A screen for genetic regulators of this avoidance behavior toward Methylobacterium identified the AWB/AWC sensory neurons and the odr-1 guanylate cyclase expressed in those four ciliated neurons as mediators of the aversive response. Metabolic profiling of the Methylobacterium diet reveals enrichment for saturated fats, and here, we show that C. elegans sense and integrate signals related to these ingested lipids that subsequently cue food-related behaviors. Moreover, disruption of endogenous lipid metabolism modifies the intensity of the avoidance from Methylobacterium, suggesting the current state of lipid homeostasis influences food preference. Taken together, our work reveals that C. elegans modify food choice contemporaneously based in part on the chemosensory capacity to detect and utilize dietary lipids, which has longevity-promoting consequences.
Tuberculosis (TB) remains a major health threat, while the increasing occurrence of drug-resistant strains underscores the need for new antitubercular drugs. A promising strategy to combat TB is based on disrupting the mycobacterial redox homeostasis by inhibiting an NADPH-dependent oxidoreductase, mycothione reductase (Mtr). Using high-throughput screening, we recently identified potent and selective Mtr inhibitors. Here we report high-resolution X-ray structures of Mtr from Mycobacterium tuberculosis and Mycobacterium xenopi, including the M. tuberculosis enzyme complexed with a novel inhibitor, Respiri-1093. Our findings demonstrate that Respiri-1093 competes with the NADP(H) binding rather than mycothione binding. Analysis of the binding site explains the observed selectivity of the inhibitor towards the M. tuberculosis enzyme. These results provide a structural basis for rational drug design.
The EVH1 domain of the Homer1 scaffold protein interacts with the proline-rich region of Shank3, forming a key network within the postsynaptic density. While two mutations (M65I and S97L) in the EVH1 domain have been suggested to be associated with autism spectrum disorder, our results show that neither mutation has a substantial effect on the overall structure or the partner binding properties of Homer1. Compared to the S97L variant, the M65I mutant exhibits larger chemical shift perturbations both upon the mutation itself and during partner binding, while also showing signs of thermal destabilization. Finally, integration of computational and NMR data suggests that both mutations perturb the μs-ms timescale internal motions of the EVH1 domain.