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Correction
- The FEBS Journal
-  27 September 2023
The cryo-EM structure of the BoNT/Wo-NTNH complex reveals two immunoglobulin-like domains
- The FEBS Journal
-  25 September 2023
Graphical Abstract

BoNT/Wo is a newly identified BoNT-like toxin. It forms a complex with its NTNH partner, which in traditional BoNTs exhibits a protective function. The overall structural arrangement is similar to other BoNT-NTNH complexes. However, NTNH/Wo uniquely contains two extra bacterial immunoglobulin-like domains, which could be involved in toxin delivery to the target cells. Mass photometry revealed that the BoNT/Wo-NTNH/Wo complex is stable under acidic conditions and dissociates at neutral to basic pH.
An innate immune sensor wandering around – NOD1 promotes cell migration via non-canonical signaling
- The FEBS Journal
-  21 September 2023
Graphical Abstract

NOD1 is a cytosolic immune receptor that recognizes intracellular bacteria, inducing innate immune responses. Upon ligand binding, it forms a complex with RIPK2 to activate NF-κB. Additionally, NOD1 has been associated with cancer progression. Hezinger et al. investigated a non-canonical role of NOD1 in cell migration and discovered that Nod1 is crucial for the migration and chemotaxis of HeLa cells and identified HAX-1 as a novel interaction partner.
Comment on: https://doi.org/10.1111/febs.16912.
The regulation of liquid‐liquid phase separated condensates containing nucleic acids
- The FEBS Journal
-  21 September 2023
Graphical Abstract

Condensates are formed by liquid–liquid phase separation, and mediated by weak, multivalent intermolecular interactions. In condensates, biomolecules have high concentrations, and many biological processes involving nucleic acids occur. In this review, we mainly summarize the regulation of phase-separated condensates containing nucleic acids by the nature of proteins and the properties of nucleic acids, and speculate the possible potential of phase-separated condensates as a drug target.
Seek and you shall find—news on the quest for novel PET-degrading enzymes
- The FEBS Journal
-  20 September 2023
Graphical Abstract

Plastic-degrading enzymes hold promise for eco-friendly recycling methods. However, their catalytic rates are inadequate to degrade the millions of tons of plastic waste produced yearly. Zhang et al. reported the discovery of PET40, a versatile PET-hydrolyzing esterase. While PET40 has a comparably low hydrolytic activity on PET, they demonstrate its broad activity on an expanded substrate pool, shedding light on its potential ecological role and suggesting that PET might be only a recent addition to its substrate spectrum.
Comment on: https://doi.org/10.1111/febs.16924.
GR-KLF15 pathway controls hepatic lipogenesis during fasting
- The FEBS Journal
-  13 September 2023
Graphical Abstract

During fasting, the body stops lipogenesis by suppressing sterol regulatory element-binding protein-1 (SREBP-1). Fasting-induced Kruppel-like factor 15 (KLF15) interacts with liver X receptor to regulate SREBP-1 expression. Glucocorticoid receptor (GR) induces KLF15 and suppresses lipogenesis via KLF15-SREBP-1. The necessity of KLF15 for SREBP-1 suppression was confirmed in a KLF15 knockout mouse model. Thus, the hypothalamic–pituitary–adrenal-axis-regulated GR-KLF15 pathway plays a critical role in the regulation of lipid metabolism in the fasting liver.
Corrigendum
- The FEBS Journal
-  12 September 2023
Novel tetrahydrofolate-dependent d-serine dehydratase activity of serine hydroxymethyltransferases
- The FEBS Journal
-  12 September 2023
Graphical Abstract

In addition to their canonical hydroxymethyltransferase activity, human and E. coli serine hydroxymethyltransferases (SHMTs) were found to exhibit novel d-serine dehydratase activity, which degrades d-serine to pyruvate and ammonia and requires tetrahydrofolate. This activity is critical, because the growth of an SHMT-deficient E. coli strain was significantly impaired in the presence of d-serine. We propose a possible reaction mechanism for d-serine dehydration by SHMTs and suggest that they play an important physiological role in d-serine metabolism.
From molecular basis to clinical insights: a challenging future for the vitamin D endocrine system in colorectal cancer
- The FEBS Journal
-  12 September 2023
Graphical Abstract

Here, we review the variety of molecular mechanisms underlying the antitumor effects of the vitamin D endocrine system in colorectal cancer (CRC), which affect multiple processes that are dysregulated during tumor initiation and progression. Additionally, we discuss the epidemiological data that associate vitamin D deficiency and CRC, and the most relevant randomized controlled trials of vitamin D3 supplementation conducted in both healthy individuals and CRC patients.
Simultaneous structural replacement of the sphingoid long‐chain base and sterol in budding yeast
- The FEBS Journal
-  10 September 2023
Graphical Abstract

The basic structures of sphingolipids and sterols differ among species; however, the physiological significance is not well understood. In this study, we performed simultaneous replacement of long-chain base structure of sphingolipids and sterol to mammalian types in budding yeast and found that the simultaneous replacement can compensate the growth of yeast but causes multiple stress hypersensitivity and abnormal plasma membrane and cell wall properties.
Functional and structural properties of pyridoxal reductase (PdxI) from Escherichia coli: a pivotal enzyme in the vitamin B6 salvage pathway
- The FEBS Journal
-  21 September 2023
Synaptotagmin‐7 Mediates Cardiac Hypertrophy by Targeting Autophagy
- The FEBS Journal
-  19 September 2023
Yeast mitochondria can process de novo designed β-barrel proteins
- The FEBS Journal
-  18 September 2023
Sleep apnoea, gut dysbiosis and cognitive dysfunction
- The FEBS Journal
-  15 September 2023
A CRISPR/Cas9-based multicopy integration system for protein production in Aspergillus niger
- The FEBS Journal
-  19 June 2023
Graphical Abstract

Using an iterative two-step CRISPR/Cas9-mediated genome editing approach, 10 loci were modified to generate multi-copy strains expressing the gene of interest in the filamentous fungus Aspergillus niger. The selected loci for gene disruption represent highly expressed genes encoding extracellular proteins including the major starch degrading enzymes and proteases. We successfully used the expression platform to generate multicopy A. niger strains producing the Penicillium expansum PatE protein.
New insights into the function and pathophysiology of the ectodomain sheddase A Disintegrin And Metalloproteinase 10 (ADAM10)
- The FEBS Journal
-  22 May 2023
Graphical Abstract

There is an increasing appreciation that the A Disintegrin And Metalloproteinase 10 (ADAM10) is of importance in health and disease. This review aims to summarize recent findings referring to the cell biology and pathophysiological implications of ADAM10. Its role in common and rare diseases is discussed here, with the goal to unravel ADAM10's translational potential as a target for pharmacological intervention or its use as a biomarker.
Caspase cleaves Drosophila BubR1 to modulate spindle assembly checkpoint function and lifespan of the organism
- The FEBS Journal
-  4200-4223
-  7 May 2023
Graphical Abstract

Caspases cleave hundreds of substrates in both lethal and non-lethal scenarios. However, physiological consequences of substrate cleavage are poorly described. Here, Natsuki Shinoda, Masayuki Miura and colleagues found that caspases cleave Drosophila BubR1, a spindle assembly checkpoint component. They showed that Drice, but not Dcp-1, is in proximity to BubR1, suggesting that protein proximity facilitates substrate preference. The cleaved fragments displayed altered subcellular localization and protein–protein interactions. Flies harboring cleavage-resistant BubR1 showed longer duration of BubR1 localization to the kinetochore, as well as extended lifespan. In conclusion, the caspase-mediated cleavage of BubR1 limits spindle assembly checkpoint and organismal lifespan.
Efficient CRISPR/Cas9 mediated large insertions using long single-stranded oligonucleotide donors in C. elegans
- The FEBS Journal
-  4429-4439
-  31 May 2023
Graphical Abstract

Highly efficient CRISPR/Cas9 genome editing in Caenorhabditis elegans has been facilitated by using single-stranded oligonucleotide donors as repair templates. However, insertion of larger sequences remains challenging. Here, Matthew Eroglu, Bin Yu and Brent Derry simplified the generation of long ssDNA as donors in CRISPR/Cas9. High ssDNA yields are rapidly generated using a standard PCR followed by an enzymatic digest with lambda exonuclease. The insertion frequency for these long ssDNA donors is remarkably higher than dsDNA. This can be leveraged to simultaneously generate multiple large insertions and successful edits. This approach enables highly efficient insertion of longer sequences using CRISPR/Cas9 in C. elegans.
Unravelling the complexity of enzyme catalysis
- The FEBS Journal
-  2204-2207
-  3 May 2023
Graphical Abstract

The field of enzymology has witnessed landmark developments that have led to its improved understanding at the molecular level and to the discovery of complex relationships between enzyme structures, catalytic mechanisms and biological function. How enzymes are regulated at the gene and post-translational levels and how catalytic activity is controlled are topical areas of the study. Here, Nigel Scrutton introduces The FEBS Journal's Focus Issue on Enzymes, which features breaking science and informative reviews, as well as personal reflections, and illustrates the breadth and importance of contemporary molecular enzymology research.
Hypoxia-inducible lncRNA MIR210HG promotes HIF1α expression by inhibiting miR-93-5p in renal tubular cells
- The FEBS Journal
-  4040-4056
-  8 April 2023
Notch signalling: multifaceted role in development and disease
- The FEBS Journal
-  11 May 2023
Graphical Abstract

Notch signalling is an evolutionarily conserved pathway that plays a fundamental role in various developmental events. Involvement of the same pathway in several diverse cellular processes is only possible because of the complex regulatory mechanisms of the pathway. In this review, we provide an overview of the mechanism and regulation of the Notch signalling pathway along with its multifaceted functions in different aspects of development and disease.
Structure and epitope of a neutralizing monoclonal antibody that targets the stem helix of β coronaviruses
- The FEBS Journal
-  3422-3435
-  4 April 2023
Graphical Abstract

The development of broadly neutralizing antibodies (BNAbs) against β-coronavirus (βCoV) is important for developing variant-proof therapeutics and vaccines. 1249A8 is a BNAb that targets the stem helix (SH) of βCoV spike proteins. Crystal structure analysis of the 1249A8/MERS-CoV SH complex, and comparisons with other SH-targeting BNAbs, identifies key molecular features of this antibody class that are required for broad-spectrum neutralization of SARS-CoV-1, SARS-CoV-2, and MERS-CoV.
Glycosylation increases active site rigidity leading to improved enzyme stability and turnover
- The FEBS Journal
-  3812-3827
-  2 April 2023
Graphical Abstract

Glycosylation is one of the most common post-translational modifications in nature. Yet, its impact on the enzyme structure–function relationship is limited. Using a combination of experimental and computational modelling, we found that the haem-enzyme horseradish peroxidase becomes more rigid on glycosylation. Rather than increased rigidity impeding catalysis as per the classic ‘activity-stability trade-off’ idea, glycosylation increases turnover by 10-fold and makes the enzyme more stable.
The role of lysosomal membrane proteins in autophagy and related diseases
- The FEBS Journal
-  23 May 2023
Targeting cellular senescence with senotherapeutics: senolytics and senomorphics
- The FEBS Journal
-  1362-1383
-  11 January 2022
Graphical Abstract

Cellular senescence, a critical hallmark of ageing, has been shown to drive many age-associated chronic diseases. Senescent cells (SnCs) up-regulate pathways associated with evasion of apoptosis, survival, senescence-associated secretory phenotype (SASP) development and others that are targeted using senotherapeutics. Senotherapeutics selectively target SnCs for their clearance (senolytics) or suppression of their SASP (senomorphics). Many studies have demonstrated the benefit of senotherapeutic treatment for the extension of health and lifespan.
The mitochondrial permeability transition: Recent progress and open questions
- The FEBS Journal
-  7051-7074
-  28 October 2021
Graphical Abstract

The mechanistic basis for the mitochondrial permeability transition (an inner membrane permeability increase that is a causative event in cell death) has puzzled mitochondrial research for 70 years. Here, we review the field and discuss recent evidence on how a Ca2+-dependent conformational change of F-ATP synthase and of adenine nucleotide translocator may transform these energy-conserving devices into energy-dissipating multiconductance channels causing the permeability transition.
The blood–retina barrier in health and disease
- The FEBS Journal
-  878-891
-  18 December 2021
Graphical Abstract

The inner blood–retina barrier (iBRB) refers to the properties of endothelial cells associated with the blood vessels of the inner retina. These cells strictly regulate entry and exit from the retina and perturbations in their function have detrimental effects on vision and lead to conditions such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). This review provides a succinct overview of BRB breakdown-associated retinal conditions and the putative underlying mechanisms of disease.
Cellular senescence: all roads lead to mitochondria
- The FEBS Journal
-  1186-1202
-  20 January 2022
Graphical Abstract

Mitochondria play a central role in the development of cellular senescence. Senescence is characterized by several mitochondrial functional changes such as a decrease in OXPHOS, reduced levels of NAD+ and ATP, and accumulation of TCA cycle metabolites, DAMPs, and ROS. Here, we provide an overview of the recent findings demonstrating how these mitochondrial changes can contribute to the senescence-associated growth arrest and the SASP.
Nrf2 and oxidative stress in liver ischemia/reperfusion injury
- The FEBS Journal
-  5463-5479
-  30 December 2021
Graphical Abstract

Nrf2 activates different cellular mechanisms in response to ischemia-reperfusion (IR) injury in liver. IR is a major cause of graft loss and dysfunction in clinical transplantation and organ resection. During the IR process, ROS generation leads oxidative stress, inflammation and mitochondrial dysfunction. After Nrf2 activation, the downstream antioxidant upregulation can act as a primary cellular defense and help to promote hepatic recovery during IR.
Lipid metabolism and Alzheimer's disease: clinical evidence, mechanistic link and therapeutic promise
- The FEBS Journal
-  1420-1453
-  7 January 2022
Graphical Abstract

Alzheimer’s disease (AD) is a neurodegenerative disease with multifactorial etiology, intersecting risk factors, and a lack of disease-modifying therapeutics. In this review, converging clinical evidence defining lipid dyshomeostasis in early stages of AD is summarized followed by discussions on mechanisms by which lipid metabolism contributes to pathogenesis and modifies disease risk. Furthermore, existing and potential lipid-targeting therapeutic strategies are reviewed.
FOXOs: masters of the equilibrium
- The FEBS Journal
-  7918-7939
-  5 October 2021
Graphical Abstract

Changes in the extracellular and intracellular environment cause ‘cellular stress’ that is potentially detrimental and can force an equilibrium shift from healthy to diseased and eventually organismal death. Forkhead box O (FOXO) transcription factors are regulators of the equilibrium and ensure optimal cellular function and lifespan. There are four FOXO isoforms, and hence, the question addressed here: Do FOXOs act to preserve the equilibrium as a family or in an isoform-specific manner?
A guide to studying protein aggregation
- The FEBS Journal
-  554-583
-  4 December 2021
Graphical Abstract

The accumulation of un- or misfolded proteins can lead to the formation of amorphous or ordered aggregates. Protein aggregation is often associated with human diseases and unravelling its underlying mechanism is critical for the development of diagnostic methods or treatments. However, investigating protein aggregation is challenging due to its complex and dynamic nature. Here, we summarized some popular methods to study the various aspects and steps involved in protein aggregation.
Ferroptosis: regulation by competition between NRF2 and BACH1 and propagation of the death signal
- The FEBS Journal
-  1688-1704
-  2 February 2022
Graphical Abstract

Ferroptosis is regulated by two transcription factors, NRF2 and BACH1, as its suppressor and promoter respectively. Here, we reviewed how these factors regulate execution of ferroptosis by changing ferroptosis-related metabolites (labile iron, glutathione and ubiquinol), lipid metabolism and cell differentiation. Ferroptosis is elaborately regulated by the competition of NRF2 and BACH1. Death signal is secreted from ferroptotic cells to surrounding cells, and its nature is also discussed.
Interferon‐γ induces retinal pigment epithelial cell Ferroptosis by a JAK1‐2/STAT1/SLC7A11 signaling pathway in Age‐related Macular Degeneration
- The FEBS Journal
-  1968-1983
-  6 November 2021
Graphical Abstract

IFN-γ downregulates the expression of SLC7A11 via JAK1-2/STAT1 signaling pathway, which results in decreases in cysteine transport and, subsequently, decreased GSH synthesis. Simultaneously, IFN-γ increases intracellular Fe2+ levels through the inhibition of SLC40A1. GSH depletion and Fe2+ accumulation cause retinal pigment epithelial cells ferroptosis and accelerate the progression of AMD.