The ubiquitin-like protein ISG15 is activated in response to type 1 interferons and its conjugation to proteins regulates the response to bacterial and viral infection. Its subsequent deconjugation, which is broadly achieved by the human enzyme USP18, critically controls interferon signaling and the defense against pathogens. However, the molecular determinants underlying USP18 specificity for ISG15

Hydrogen (H) atoms account for about half the atoms in biomacromolecules and are essential for their biochemical properties such as enzymatic functions. Obtaining precise enzyme structures that include all the H atoms allows a deeper understanding of their structure-function relationships. Copper-containing nitrite reductases (CuNIRs) catalyze transformation of nitrite to nitric oxide, which has impacts

Unlike terrestrial environments, where humans reside, there is no sunlight in the deep sea. Instead, dim visible light from black-body radiation and bioluminescence illuminates hydrothermal vent areas in the deep sea. A deep-sea hydrothermal vent shrimp, Rimicaris hybisae, is thought to detect this dim light using its enlarged dorsal eye; however, the molecular basis of its photoreception remains unexplored

tRNAs are central players in translation, delivering cognate amino acids to the ribosome. To fulfill this essential function, secondary and tertiary structures of tRNAs are highly conserved. In metazoan, however, several mitochondrial tRNAs show strong structural deviations and lack D- or T-arms. As these elements are important for the interaction with tRNA-binding proteins, these proteins are adapted

ROCK1 plays an important role in phagocytosis by inducing cytoskeletal rearrangement. Although the transcriptional regulation of ROCK1 is known but its post-transcriptional regulation is underexplored. We intended to find a mechanism of microglial phagocytosis through possible post-transcriptional regulation of ROCK1. The study identified miR-129-5p as a regulator of microglial phagocytosis following

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by loss of dopaminergic neurons, particularly in the substantia nigra of the brain. α-Synuclein is a major causative factor in both familial and sporadic forms of PD, and its protein aggregates play critical roles in neuronal cell death and PD pathogenesis. This study explored the role of ubiquitin-specific protease

Syntenin-1 is a promising therapeutic target for cancer, as its inhibitors have shown positive efficacy in preclinical models of various cancer types. Posttranslational modifications including phosphorylation play an important role in regulating syntenin-1 activity, but the underlying molecular mechanisms have not been completely understood. To figure out the enzymes that catalyze syntenin-1 modifications

Vancomycin-resistant enterococci (VRE) are high-priority targets for new therapeutic development. In VRE, expression of the resistance phenotype is controlled by the VanRS two-component system, which senses the presence of the antibiotic and responds by initiating transcription of resistance genes. VanS is a transmembrane sensor histidine kinase that is known to detect the antibiotic and then transduce

Major Histocompatibility Complex I (MHC-I) and MHC-I-like molecules play a central role in mediating immunity. Through their conservation across all taxa of jawed vertebrates, the MHC-I-like proteins have adapted to present non-peptidic antigens to distinct T cell populations. While our understanding of the structure-function relationship of MHC-I and MHC-I-like molecules in humans and mice is well

PARP4 is an ADP-ribosyltransferase typically associated with the cytoplasmic vault organelle. PARP4 has a distinct domain composition relative to other PARP enzymes; however, the N-terminal region of PARP4 is homologous to a collection of domains found in PARP1, a regulator of multiple nuclear processes including the cellular response to DNA damage. The N-terminal region of PARP4 interacts in vitro

In their mammalian hosts, African trypanosomes abundantly express GPI-anchored variant surface glycoproteins (VSGs) on their cell surfaces. These provide a protective surface coat that has been studied best in Trypanosoma brucei. The genome of this single-celled parasite contains more than 2000 VSG genes and pseudogenes, a rich foundation based on which only one functional VSG is expressed at any given

The importance of phosphatidylinositol 3,4,5- trisphosphate (PIP3) in cell signaling has been well established. Despite phosphatidylinositol 3,4-bisphosphate [PI(3,4)P2] emerging as an actor independent of PIP3, its exact signaling role remains poorly understood and the precise dynamics of PI(3,4)P2 and PIP3 upon receptor tyrosine kinase (RTK) stimulation are still inadequately investigated. In this

Sirtuin 2 (SIRT2) is a ubiquitously expressed cellular enzyme that deacylates protein lysine residues using NAD+ as a cofactor. SIRT2-mediated post-translational modifications on a plethora of protein targets position the enzyme to exert a wide-ranging regulatory role in many physiological and pathological processes. More than 39 SIRT2 crystal structures in complex with substrates, products, mimetics

Diabetic cardiomyopathy (DCM) is a myocardial structural and functional abnormality directly caused by diabetes and is a principal factor in the development of cardiovascular complications in patients with diabetes. The study aims to investigate the role of circOGDH in the development of DCM and elucidate its precise underlying mechanisms. We established two well-characterised diabetic mouse models

The SEL1L-HRD1 complex is a critical component of the endoplasmic reticulum (ER)-associated protein degradation (ERAD) pathway, essential for maintaining ER homeostasis and cellular function. While the crucial roles of SEL1L and HRD1 in various physiological processes have been reported in mice and humans, their specific functions in male germ cells remain unexplored. Here, we show that, while SEL1L

Obese individuals are categorized as either "Metabolically Abnormal Obesity" (MAO) or "Metabolically Healthy Obesity" (MHO) based on their insulin resistance and metabolic disorders. However, the intrinsic mechanism remains largely unknown. Through examining gut microbiota and fecal metabolome of MAO and MHO patients, we identified intestinal microorganism Ruminococcus torques (R. torques) and its

Transient receptor potential canonical 6 (TRPC6) is a receptor-operated nonspecific cation channel. To date, more than 30 TRPC6 variants have been reported to focal segmental glomerulosclerosis (FSGS), which can present from infancy to adulthood and is characterized by proteinuria and often nephrotic syndrome leading to kidney failure. These variants may exhibit gain-of-function (e.g. K874X) or loss-of-function

The small GTPases Arf, Ras, and Rho cycle between their active GTP-bound and inactive GDP-bound forms. Their effector proteins or inorganic redox agents regulate this cycle, which in turn regulates various important cell signals. Unlike effector protein-based regulation, redox-mediated regulation that occurs through the redox response of small GTPases to a redox agent is feasible only when the small

Models of Ab-antigen complexes can be used to understand interaction mechanisms and for improving affinity. This study evaluates the use of the protein structure prediction algorithm AlphaFold (AF) for exploration of interactions between peptide epitope tags and the smallest functional antibody fragments, nanobodies (Nbs). Although past studies of AF for modeling antibody-target (antigen) interactions

Matrix metalloproteinase-9 (MMP-9) is a critical enzyme involved in extracellular matrix degradation and is strongly implicated in many diseases, including triple-negative breast cancer and other poor prognosis cancers. Selective inhibition of MMP-9 is therefore a promising therapeutic strategy. However, development of MMP inhibitors has been hindered by challenges in achieving specificity, with past

The Arabidopsis blue light photoreceptor cryptochrome 2 (CRY2) responds to blue light to initiate a variety of plant light-based behaviors and has been widely used for optogenetic engineering. Despite these important biological functions, the precise photoactivation mechanism of CRY2 remains incompletely understood. In light, CRY2 undergoes tetramerization and binds to partner proteins, including the

Luminal type breast cancer (BrCa) cells invade into the surrounding tissues as collective strands, making them more metastatic than single cells. We have previously reported that the leading subpopulation of collective cells expressed high levels of CD44, which was associated with enhanced migratory and invasive potential of BrCa. It is crucial to elucidate how CD44 becomes enriched in leader cells

Pancreatic β-cells play a critical role in glucose homeostasis by secreting insulin. Chronic oxidative stress causes β-cell dysfunction, including β-cell loss; however, the underlying mechanisms remain unclear. Here, we demonstrate the critical role of the regulated in development and DNA damage response 2 (REDD2/DDiT4L/Rtp801L) in β-cell dysfunction. In INS-1 β-cells, Redd2 was induced by high glucose/palmitate

The Hippo signaling pathway is crucial in pathological functions such as tumors. Yes-associated protein (YAP), a well-known downstream effector of the Hippo pathway, has been intensively studied; emerging evidence suggests that multiple cell membrane receptors can regulate the Hippo pathway. However, the mechanistic roles of these upstream pathways remain largely unknown. Here, we identified the β-galactoside

The mitochondrial enzyme, glutamic-oxaloacetic transaminase (GOT2), catalyzes the reaction between oxaloacetate and glutamate generating aspartate and alpha-ketoglutarate (α-KG). Glutamate can also be directly converted to α-KG by glutamate dehydrogenase. We investigated mitochondrial and systemic effects of an inducible liver specific-mouse GOT2 knockout (KO). We observed no differences in body mass

Mammalian α-arrestins are members of the same arrestin family as the ubiquitously expressed and extensively studied β-arrestins. Arrestins share common structural elements including the conserved N- and C-arrestin-fold domains, polar core, finger loop, and C-terminal tail, all of which mediate protein-protein interactions. In β-arrestins, these domains enable the control of G protein-coupled receptor

Topical application of natural phenolic compound rosmarinic acid (ROSA) and its analogues is known to exert pharmacological effects, including anti-inflammation, anti-allergy, antioxidant properties. However, the mechanism of action of the ROSA remains largely unknown. Here, we describe a novel role of natural phenolic rosmarinic acid and its analogues in the selective inhibition of warmth-sensitive

Profilin 1 (PFN1) is a key cytoskeletal protein that regulates actin dynamics by incorporating monomeric actin into linear filaments. PFN1 deletion or mutations have been linked to numerous neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). However, the contribution of PFN1 to neurodegenerative pathologies is poorly understood. Recent studies have implicated the role of aberrant

Pseudouridine (Ψ) is one of the most abundant RNA modifications. Following RNA degradation, Ψ nucleotides are dephosphorylated and catabolized into uracil and ribose 5'-phosphate via a two-step enzymatic reaction catalyzed by enzymes present in many bacteria and eukaryotes, but not in mammals. Malfunction of Ψ catabolism has adverse physiological effects in plants. In humans, the enzyme HDHD1A dephosphorylates

Biofuel production from lignocellulosic biomass offers a transformative solution to reduce global fossil fuel dependency. Certain thermophilic anaerobes, including Clostridium thermocellum, show promise for renewable ethanol production due to their ability to break down plant material at high temperatures. However, achieving commercially viable ethanol yields has proven challenging despite extensive

Heat shock protein 90 (Hsp90) is a vital molecular chaperone that is essential for activating a diverse array of regulatory proteins through an ATP-dependent clamping cycle. The Hsp90 clamping cycle is driven by large-amplitude conformational changes within the N-terminal ATPase domain, including the release of an autoinhibitory N-terminal β-strap followed by a less well-characterized ATP gate rearrangement

The persistently low success rate of human in vitro fertilization (IVF) remains a major clinical challenge, despite significant technological advancements. While culture media composition is known to influence outcomes, the specific components affecting embryonic development are poorly understood. In this study, we identify N-glycolylneuraminic acid (Neu5Gc), a foreign sialic acid contaminant prevalent

Biological membranes, which comprise proteins, lipids and glycans, serve as essential gatekeepers protecting cells from the external environment. In bacteria, phospholipids are a major class of membrane lipids, whose biology has extensively been studied in the Gram-negative organism Escherichia coli. As an adaptive mechanism, E. coli dynamically remodels its phospholipids in response to its environment

Phosphatases of regenerating liver (PRL or PTP4A) are protein phosphatases implicated in cell growth, magnesium homeostasis, and cancer metastasis. During catalysis, a phosphocysteine intermediate forms, which must undergo hydrolysis to regenerate the active enzyme. In addition to dephosphorylating substrates, PRLs act as pseudo-phosphatases and bind CBS-pair domain divalent metal cation transport

Neurons depend on microtubule organization for axon and dendrite formation during differentiation. Yet, our understanding of how microtubules are remodelled during this process is far from complete. Echinoderm microtubule-associated protein-like (EML) is a family of microtubule-associated proteins (MAPs) highly expressed in neuronal cells. Database analysis revealed that EMLs are subject to alternative

Hyperuricemia is independently associated with an increased risk of nonalcoholic steatohepatitis (NASH), but the underlying mechanisms responsible for this association remain unclear. We first analyzed the association between intrahepatic UA levels and gasdermin D (GSDMD)-mediated pyroptosis in vivo and in vitro. We subsequently generated hepatic-specific glucose transporter 9 (GLUT9)-knockout mice

Replication Protein A (RPA), a single-stranded DNA (ssDNA) binding protein, is vital for various aspects of genome maintenance such as replication, recombination, repair, and cell cycle checkpoint activation. Binding of RPA to ssDNA protects it from degradation by cellular nucleases, prevents secondary structure formation, and suppresses illegitimate recombination. In our current study, we identified

Common Fragile Sites (CFSs) are chromosomal loci with inherent characteristics that make them difficult to fully replicate thus rendering them vulnerable to replication stress (RS). Under-replicated CFSs manifest as cytogenetic gaps and breaks on metaphase chromosomes. Moreover, CFSs are hotspots for tumorigenic chromosomal rearrangements. The Fanconi anemia (FA) pathway is at the core of a network

Calpain-1 and calpain-2 are heterodimeric proteases consisting of a common small regulatory subunit CAPNS1 and a large catalytic subunit, CAPN1 or CAPN2, respectively. These calpains have emerged as potential therapeutic targets in cancer and other diseases through their roles in cell signaling pathways affecting sensitivity to chemotherapeutic and targeted drugs, and in promoting metastasis. While

The role of circadian clocks in regulating metabolic processes is well known; however, their impact on metabolic states across species and life stages remains largely unexplored. This study investigates the relationship between circadian rhythms and metabolic regulation in the Drosophila larval fat body, a metabolic hub analogous to the mammalian liver and adipose tissue. Surprisingly, the fat body

Porcine reproductive and respiratory syndrome virus (PRRSV) exhibits rapid evolution due to its high mutation rate and frequent recombination, posing significant challenges for disease control. In this study, we investigated the molecular mechanisms underlying strain-specific variations in PRRSV replication phenotypes. Using reverse genetics and molecular biology approaches, we established a non-infectious

ANRIL, also referred to as CDKN2B-AS1, is a lncRNA gene implicated in the pathogenesis of multiple human diseases including atherosclerotic coronary artery disease, however, definitive in vivo evidence is lacking and the underlying molecular mechanism is largely unknown. In this study, we show that ANRIL overexpression causes atherosclerosis in vivo as transgenic mouse overexpression of full-length

Research into the role of chronic sterile inflammation (i.e., a prolonged inflammatory state not caused by an infectious agent) in vascular disease progression has continued to grow over the last few decades. DAMPs have a critical role in this research due to their ability to link stress-causing cardiovascular risk factors to inflammatory phenotypes seen in vascular disease. In this mini-review, we

Women develop alcohol-associated liver disease (ALD) faster than men at any level of alcohol consumption, implicating estrogen as a contributing factor. However, the precise mechanism remains unknown. Therefore, 12-week-old female C57BL/6N mice were subjected to either bilateral ovariectomy (OVX) or sham surgery. After a 3-week recovery period, the mice were fed either a 5% ethanol (EtOH)-containing

Histone proteolysis is sometimes described as an extreme post-translational modification (PTM), as it removes both a stretch of histone sequence and any PTMs that were previously added to it. Such an acute and significant loss of information could trigger many different downstream effects, making it attractive as a mechanism for rapid gene silencing or activation. Yet, protease activity is challenging

Radiotherapy plays a critical role in treating esophageal cancer, but individual responses vary significantly, impacting patient outcomes. This study integrates machine learning–driven multimodal radiomics and transcriptomics to develop predictive models for radiotherapy sensitivity and prognosis in esophageal cancer. We applied the SEResNet101 deep learning model to imaging and transcriptomic data

Cyanobacterial photosystem I (PSI) can undergo modifications that adjust photosynthetic electron transport in response to fluctuations in environmental and cellular conditions. We recently reported that PSI isolated from Synechocystis sp. PCC 6803 (S. 6803) strains lacking a peripheral oxygen reduction reaction (ORR1) pathway demonstrated altered P700 photooxidation capacity, changes in spectral properties

Linking genotype to phenotype is a central goal in biology. In the microbiological field, transposon mutagenesis is a technique that has been widely used since the 1970s to facilitate this connection. The development of modern “omics approaches and next-generation sequencing have allowed high-throughput association between genes and their putative function. In 2009, four different variations in modern

Epitope tags are a simple and versatile way to label proteins, as their sequences can easily be inserted into protein coding sequences so that the expressed proteins will bear the tag(s). These tags can be used to identify and purify proteins in vitro using Western blots, flow cytometry, affinity chromatography, and other techniques. When labeled with a fluorescent probe, tagged proteins can be visualized

Glycosylphosphatidylinositol (GPI) serves as a membrane anchor of numerous cell surface proteins. It is synthesized in the endoplasmic reticulum from phosphatidylinositol (PI) by stepwise reactions and transferred to the C terminus of the protein. Defects in genes involved in GPI biosynthesis affect the expression of GPI-anchored proteins or their structure, causing the neurological disorder, inherited

Cardiolipin (CL), the signature phospholipid of mitochondria, carries four fatty acids that are remodeled after de novo synthesis. In yeast, remodeling is accomplished by the joint action of Cld1, a lipase that removes a fatty acid from CL, and Taz1, a transacylase that transfers a fatty acid from another phospholipid to monolysocardiolipin (MLCL). While taz1 homologs have been identified in all eukaryotes

Triple-negative breast cancer (TNBC) is a highly aggressive disease with limited approved therapeutic options. The rapid growth and genomic instability of TNBC cells make mitosis a compelling target, and a current mainstay of treatment is paclitaxel (Ptx), a taxane that stabilizes microtubules during mitosis. While initially effective, acquired resistance to Ptx is common, and other antimitotic therapies

N-Myc downstream regulated gene-1 (NDRG1) and the other three members of this family (NDRG2, 3, and 4) play various functional roles in the cellular stress response, differentiation, migration, and development. These proteins are involved in regulating key signaling proteins and pathways that are often dysregulated in cancer, such as EGFR, PI3K/AKT, c-Met, and the Wnt pathway. NDRG1 is the primary

Vinculin (Vcn) and its splice variant metavinculin (MVcn) are cell adhesion proteins that regulate cell morphology, adhesion, and motility. They function as scaffold proteins that anchor membrane receptors to filamentous actin (F-actin) at focal adhesions and cell–cell junctions. MVcn bears an extra 68 amino acid insert in the tail domain and is selectively expressed in cardiac and smooth muscle cells

Environmental nutrient levels affect cancer cell metabolism, activating adaptive mechanisms in cancer cells to deal with nutrient stress. However, it remains unclear how tumor cells sustain survival under nutrient-stress circumstances through metabolic reprogramming. Our study focused on nutrient deficiency-induced oxidative damage, revealing that increased expression of the iron-sulfur cluster assembly

Water use efficiency is an important target for breeding of improved drought resistance. Minimizing leaf transpirational water loss plays a key role in drought resistance. But this reduces CO2 levels in leaves, which often reduces photosynthetic efficiency and yield. Signaling pathways play important roles in stress responses, and identifying the molecular, biochemical, and physiological determinants

The peripheral immune system has a strong effect on the central nervous system (CNS). Systemic lipopolysaccharides (LPS) administration triggers robust microglial activation and induces significant inflammatory responses in the hippocampus. This study investigates the role of Transforming Growth Factor-β-Activated Kinase 1 (TAK1) in mediating LPS-induced hippocampal neuroinflammation and cognitive

Global food shortages and rising antimicrobial resistance require alternatives to antibiotics and agrichemicals for the management of agricultural bacterial pathogens. The phytopathogen Pseudomonas syringae pv. actinidiae (Psa) is the causal agent of kiwifruit canker and is responsible for major agricultural losses. Bacteriophage enzymes present an emerging antimicrobial option. Endolysins possess

Disruptions in testicular homeostasis can lead to impaired spermatogenesis and male infertility. Such disturbances may result from various factors, including viral or bacterial infections, toxic injuries, and genetic mutations or deletions. The maintenance of testicular homeostasis is governed by a complex interplay of various cells, hormones, paracrine factors, genes, and enzymes. UCHL1, a member

Cholesterol-loaded macrophage foam cells are a key feature of atherosclerotic plaques. Oxysterol-binding protein-related protein 2 (ORP2) facilitates the transport of cholesterol from lysosomes to the plasma membrane in cultured cell lines. However, the role of ORP2 in macrophages and its involvement in atherosclerosis remain unclear. In this study, we found ORP2 expression was reduced in atherosclerotic