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Target-locked: a mechanism for disaggregase binding to aggregated proteins J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-12 Trevor M. Morey, Walid A. Houry
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Loss of the glycosyltransferase Galnt11 affects vitamin D homeostasis and bone composition J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-12 E. Tian, Caroline Rothermel, Zachary Michel, Luis Fernandez de Castro, Jeeyoung Lee, Tina Kilts, Tristan Kent, Michael T. Collins, Kelly G. Ten Hagen
O-glycosylation is a conserved post-translational modification that impacts many aspects of organismal viability and function. Recent studies examining the glycosyltransferase Galnt11 demonstrated that it glycosylates the endocytic receptor megalin in the kidneys, enabling proper binding and reabsorption of ligands, including vitamin D binding protein (DBP). -deficient mice were unable to properly
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A selection and optimization strategy for single-domain antibodies targeting the PHF6 linear peptide within the Tau intrinsically disordered protein J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-12 Justine Mortelecque, Orgeta Zejneli, Séverine Bégard, Margarida C. Simões, Lea ElHajjar, Marine Nguyen, François-Xavier Cantrelle, Xavier Hanoulle, Jean-Christophe Rain, Morvane Colin, Cláudio M. Gomes, Luc Buée, Isabelle Landrieu, Clément Danis, Elian Dupré
The use of VHHs (Variable domain of the Heavy-chain of the Heavy-chain-only antibodies) as disease-modifying biomolecules in neurodegenerative disorders holds promises including targeting of aggregation-sensitive proteins. Exploitation of their clinical values depends however on the capacity to deliver VHHs with optimal physico-chemical properties for their specific context of use. We described previously
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Resolving the polycistronic aftermath: essential role of Topoisomerase IA in preventing R-loops in Leishmania J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-12 Payel Das, Arnab Hazra, Saradindu Saha, Sadhana Roy, Mandrita Mukherjee, Saugata Hazra, H.K. Majumdar, Somdeb BoseDasgupta
Kinetoplastid parasites are ‘living bridges’ in the evolution from prokaryotes to higher eukaryotes. The near-intronless genome of the kinetoplastid , exhibit polycistronic transcription which can facilitate R-loop formation. Therefore, to prevent such DNA-RNA hybrids has retained prokaryotic-like DNA Topoisomerase IA (LdTOPIA) in course of evolution. LdTOPIA is an essential enzyme which is expressed
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Fatty acid oxidation drives mitochondrial hydrogen peroxide production by α-ketoglutarate dehydrogenase. J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-11 Cathryn Grayson, Ben Faerman, Olivia Koufos, Ryan J. Mailloux
In the present study, we examined the mitochondrial hydrogen peroxide (mHO) generating capacity of α-ketoglutarate dehydrogenase (KGDH) and compared it to components of the electron transport chain (ETC) using liver mitochondria isolated from male and female C57BL6N mice. We show for the first time there are some sex dimorphisms in the production of mHO by ETC complexes I and III when mitochondria
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Refining the identity of mesenchymal cell types associated with murine periosteal and endosteal bone J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-11 Intawat Nookaew, Jinhu Xiong, Melda Onal, Cecile Bustamante-Gomez, Visanu Wanchai, Qiang Fu, Ha-Neui Kim, Maria Almeida, Charles A. O’Brien
Single-cell RNA sequencing has led to novel designations for mesenchymal cells associated with bone as well as multiple designations for what appear to be the same cell type. The main goals of this study were to increase the amount of single cell RNA sequence data for osteoblasts and osteocytes, to compare cells from the periosteum to those inside bone, and to clarify the major categories of cell types
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The Aryl Hydrocarbon Receptor Interacting Protein in cancer and immunity: Beyond a chaperone protein for the dioxin receptor J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-11 Sarah A. Kazzaz, John Tawil, Edward W. Harhaj
The aryl hydrocarbon receptor (AhR) interacting protein (AIP) is a ubiquitously expressed, immunophilin-like protein best known for its role as a co-chaperone in the AhR-AIP-Hsp90 cytoplasmic complex. In addition to regulating AhR and the xenobiotic response, AIP has been linked to various aspects of cancer and immunity that will be the focus of this review article. Loss of function AIP mutations are
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Analysis of pressure activated Piezo1 open and subconductance states at a single channel level. J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-11 Ghanim Ullah, Elena D. Nosyreva, David Thompson, Victoria Cuello, Luis G. Cuello, Ruhma Syeda
Mechanically activated Piezo1 channels undergo transitions from closed to open-state in response to pressure and other mechanical stimuli. However, the molecular details of these mechanosensitive gating transitions are unknown. Here, we used cell-attached pressure-clamp recordings to acquire single channel data at steady-state conditions (where inactivation has settled down), at various pressures and
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KcsA-Kv1.x chimeras with complete ligand binding sites provide improved predictivity for screening selective Kv1.x blockers J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-11 Patrik Szekér, Tamás Bodó, Katalin Klima, Ágota Csóti, Nikoletta Ngo Hanh, József Murányi, Anna Hajdara, Tibor Gábor Szántó, György Panyi, Márton Megyeri, Zalán Péterfi, Sándor Farkas, Norbert Gyöngyösi, Péter Hornyák
Despite significant advances in the development of therapeutic interventions targeting autoimmune diseases and chronic inflammatory conditions, lack of effective treatment still poses a high unmet need. Modulating chronically activated T cells through the blockade of the Kv1.3 potassium channel is a promising therapeutic approach, however, developing selective Kv1.3 inhibitors is still an arduous task
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Novel class of peptides disintegrating biological membranes to aid in the characterization of membrane proteins J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-11 Václav Hořejší, Pavla Angelisová, Jana Pokorná, Tatsiana Charnavets, Oldřich Benada, Tomáš Čajka, Tomáš Brdička
Styrene-maleic acid (SMA) and similar amphiphilic copolymers are known to cut biological membranes into lipid nanoparticles/nanodiscs containing membrane proteins apparently in their relatively native membrane lipid environment. Our previous work demonstrated that membrane raft microdomains resist such disintegration by SMA. The use of SMA in studying membrane proteins is limited by its heterogeneity
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Acidity of persulfides and its modulation by the protein environments in sulfide quinone oxidoreductase and thiosulfate sulfurtransferase J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-11 Dayana Benchoam, Ernesto Cuevasanta, Joseph V. Roman, Ruma Banerjee, Beatriz Alvarez
Persulfides (RSSH/RSS) participate in sulfur metabolism and are proposed to transduce hydrogen sulfide (HS) signaling. Their biochemical properties are poorly understood. Herein, we studied the acidity and nucleophilicity of several low molecular weight persulfides using the alkylating agent, monobromobimane. The different persulfides presented similar p values (4.6-6.3) and pH-independent rate constants
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Genome-wide CRISPR activation screen identifies JADE3 as an antiviral activator of NF-kB dependent IFITM3 expression J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-09 Moiz Munir, Aaron Embry, John G. Doench, Nicholas S. Heaton, Craig B. Wilen, Robert C. Orchard
The innate immune system features a web of interacting pathways that require exquisite regulation. To identify novel nodes in this immune landscape we conducted a gain of function, genome-wide CRISPR activation screen with influenza A virus. We identified both appreciated and novel antiviral genes, including JADE3 a protein involved in directing the histone acetyltransferase HBO1 complex to modify
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YTHDF2 protein stabilization by the deubiquitinase OTUB1 promotes prostate cancer cell proliferation via PRSS8 mRNA degradation J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-09 Xuefeng Zhao, Suli Lv, Neng Li, Qingli Zou, Lidong Sun, Tanjing Song
Prostate cancer is a leading cause of cancer-related mortality in males. Dysregulation of RNA Adenine N-6 methylation (m6A) contributes to cancer malignancy. m6A on mRNA may affect mRNA splicing, turnover, transportation and translation. m6A exerts these effects, at least partly, through dedicated m6A reader proteins, including YTHDF2. YTHDF2 is necessary for development while its dysregulation is
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The Integrated Stress Response in metabolic adaptation J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-09 Hyung Don Ryoo
The Integrated Stress Response (ISR) refers to signaling pathways initiated by stress-activated eIF2‹ kinases. Distinct eIF2‹ kinases respond to different stress signals, including amino acid deprivation and mitochondrial stress. Such stress-induced eIF2‹ phosphorylation attenuates general mRNA translation and, at the same time, stimulates the preferential translation of specific downstream factors
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O-GlcNAcylation stimulates the deubiquitination activity of USP16 and regulates cell cycle progression J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-09 Jianxin Zhao, Jie Hua, Yahui Zhan, Chunxu Chen, Yue Liu, Liqian Yang, Haiying Wang, Hengbin Wang, Jing Li
Histone 2A monoubiquitination (uH2A) underscores a key epigenetic regulation of gene expression. In this report, we show that the deubiquitinase (DUB) for uH2A, Ubiquitin Specific Peptidase 16 (USP16), is modified by O-linked N-acetylglucosamine (O-GlcNAc). O-GlcNAcylation involves the installation of the O-GlcNAc moiety to Ser/Thr residues. It crosstalks with Ser/Thr phosphorylation, affects protein-protein
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Darkness inhibits autokinase activity of bacterial bathy phytochromes J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-09 Christina Huber, Merle Strack, Isabel Schultheiß, Julia Pielage, Xenia Mechler, Justin Hornbogen, Rolf Diller, Nicole Frankenberg-Dinkel
Bathy phytochromes are a subclass of bacterial biliprotein photoreceptors that carry a biliverdin IXα chromophore. In contrast to prototypical phytochromes that adopt a red-light absorbing Pr ground state, the far-red light absorbing Pfr-form is the thermally stable ground state of bathy phytochromes. Although the photobiology of bacterial phytochromes has been extensively studied since their discovery
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Restricted glycolysis is a primary cause of the reduced growth rate of zinc-deficient yeast cells J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-07 Colin W. MacDiarmid, Janet Taggart, Michael Kubisiak, David J. Eide
Zinc is required for many critical processes, including intermediary metabolism. In , the Zap1 activator regulates the transcription of ∼80 genes in response to Zn supply. Some Zap1-regulated genes are Zn transporters that maintain Zn homeostasis, while others mediate adaptive responses that enhance fitness. One adaptive response gene encodes the 2-cysteine peroxiredoxin Tsa1, which is critical to
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Cancer-associated Polybromo-1 bromodomain 4 missense variants variably impact bromodomain ligand binding and cell growth suppression J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-07 Karina L. Bursch, Christopher J. Goetz, Guanming Jiao, Raymundo Nuñez, Michael D. Olp, Alisha Dhiman, Mallika Khurana, Michael T. Zimmermann, Raul A. Urrutia, Emily C. Dykhuizen, Brian C. Smith
The Polybromo, BRG1-associated factors (PBAF) chromatin remodeling complex subunit Polybromo-1 (PBRM1) contains six bromodomains that recognize and bind acetylated lysine residues on histone tails and other nuclear proteins. PBRM1 bromodomains thus provide a link between epigenetic post-translational modifications and PBAF modulation of chromatin accessibility and transcription. As a putative tumor
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Purinergic signaling promotes premature senescence J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-07 Daniela Volonte, Cory J. Benson, Stephanie L. Daugherty, Jonathan M. Beckel, Mohamed Trebak, Ferruccio Galbiati
Extracellular ATP activates P2 purinergic receptors. Whether purinergic signaling is functionally coupled to cellular senescence is largely unknown. We find that oxidative stress induced release of ATP and caused senescence in human lung fibroblasts. Inhibition of P2 receptors limited oxidative stress-induced senescence, while stimulation with exogenous ATP promoted premature senescence. Pharmacological
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Common and varied molecular responses of Escherichia coli to five different inhibitors of the lipopolysaccharide biosynthetic enzyme LpxC J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-06 Anna-Maria Möller, Melissa Vázquez-Hernández, Blanka Kutscher, Raffael Brysch, Simon Brückner, Emily C. Marino, Julia Kleetz, Christoph HR. Senges, Sina Schäkermann, Julia E. Bandow, Franz Narberhaus
A promising yet clinically unexploited antibiotic target in difficult-to-treat Gram-negative bacteria is LpxC, the key enzyme in the biosynthesis of lipopolysaccharides (LPS), which are the major constituents of the outer membrane. Despite the development of dozens of chemically diverse LpxC inhibitor molecules, it is essentially unknown how bacteria counteract LpxC inhibition. Our study provides comprehensive
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G-site residue S67 is involved in the fungicide-degrading activity of a tau class glutathione S-transferase from Carica papaya J. Biol. Chem. (IF 5.5) Pub Date : 2024-02-28 Su-Yan Wang, Yan-Xia Wang, Sheng-Shuo Yue, Xin-Chi Shi, Feng-Yi Lu, Si-Qi Wu, Daniela D. Herrera-Balandrano, Pedro Laborda
Thiram is a toxic fungicide extensively used for the management of pathogens in fruits. Although it is known that thiram degrades in plant tissues, the key enzymes involved in this process remain unexplored. In this study, we report that a tau class glutathione -transferase (GST) from can degrade thiram. This enzyme was easily obtained by heterologous expression in , showed low promiscuity toward other
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Structure, dynamics, and redox reactivity of an all-purpose flavodoxin J. Biol. Chem. (IF 5.5) Pub Date : 2024-02-28 Sharique Khan, Ahmadullah Ansari, Monica Brachi, Debarati Das, Wassim El Housseini, Shelley Minteer, Anne-Frances Miller
The flavodoxin of CGA009 (Fld) supplies highly reducing equivalents to crucial enzymes such as hydrogenase, especially when the organism is iron-restricted. By acquiring those electrons from photodriven electron flow the bifurcating electron transfer flavoprotein, Fld provides solar power to vital metabolic processes. To understand Fld's ability to work with diverse partners, we solved its crystal
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Development of a fluorescence and quencher-based FRET assay for detection of endogenous peptide:N-glycanase/NGLY1 activity J. Biol. Chem. (IF 5.5) Pub Date : 2024-02-28 Hiroto Hirayama, Yuriko Tachida, Reiko Fujinawa, Yuka Matsuda, Takefumi Murase, Yuji Nishiuchi, Tadashi Suzuki
Cytosolic peptide:-glycanase (PNGase/NGLY1 in mammals) catalyzes deglycosylation of -glycans on glycoproteins. A genetic disorder caused by mutations in the NGLY1 gene leads to NGLY1 deficiency with symptoms including motor deficits and neurological problems. Effective therapies have not been established, though, a recent study used the administration of an adeno-associated viral vector expressing
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Complex N-glycosylation of mGluR6 is required for trans-synaptic interaction with ELFN adhesion proteins J. Biol. Chem. (IF 5.5) Pub Date : 2024-02-28 Michael L. Miller, Mustansir Pindwarawala, Melina A. Agosto
Synaptic transmission from retinal photoreceptors to downstream ON-type bipolar cells (BCs) depends on the postsynaptic metabotropic glutamate receptor mGluR6, located at the BC dendritic tips. Glutamate binding to mGluR6 initiates G-protein signaling that ultimately leads to BC depolarization in response to light. The mGluR6 receptor also engages in -synaptic interactions with presynaptic ELFN adhesion
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Correction: Protein kinase A-mediated phosphorylation of the broad-complex transcription factor in silkworm suppresses its transcriptional activity J. Biol. Chem. (IF 5.5) Pub Date : 2024-02-28 Wenliang Qian, Xiaoxu Gang, Tianlei Zhang, Ling Wei, Xinxin Yang, Zheng Li, Yan Yang, Liang Song, Peng Wang, Jian Peng, Daojun Cheng, Qingyou Xia
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ORMDL3 regulates NLRP3 inflammasome activation by maintaining ER-mitochondria contacts in human macrophages and dictates ulcerative colitis patient outcome J. Biol. Chem. (IF 5.5) Pub Date : 2024-02-27 Jyotsna Sharma, Shaziya Khan, Nishakumari C. Singh, Shikha Sahu, Desh Raj, Shakti Prakash, Pamela Bandyopadhyay, Kabita Sarkar, Vivek Bhosale, Tulika Chandra, Kumaravelu Jagavelu, Manoj Kumar Barthwal, Shashi Kumar Gupta, Mrigank Srivastava, Rajdeep Guha, Veena Ammanathan, Uday C. Ghoshal, Kalyan Mitra, Amit Lahiri
Genome-wide association studies in inflammatory bowel disease have identified risk loci in the orosomucoid-like 3 () gene to confer susceptibility to ulcerative colitis (UC), but the underlying functional relevance remains unexplored. Here, we found that a subpopulation of the UC patients who had higher disease activity shows enhanced expression of ORMDL3 compared to the patients with lower disease
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Insights into the roles of inositol hexakisphosphate kinase (IP6K1) in mammalian cellular processes J. Biol. Chem. (IF 5.5) Pub Date : 2024-02-24 Mohamed Chakkour, Miriam L. Greenberg
Inositol phosphates and their metabolites play a significant role in several biochemical pathways, gene expression regulation, and phosphate homeostasis. Among the different inositol phosphates, inositol hexakisphosphate (IP6) is a substrate of inositol hexakisphosphate kinases (IP6Ks), which phosphorylate one or more of the IP6 phosphate groups. Pyrophosphorylation of IP6 leads to the formation of
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Pre-rRNA facilitates the recruitment of RAD51AP1 to DNA double-strand breaks J. Biol. Chem. (IF 5.5) Pub Date : 2024-02-24 Linlin Chen, Xiaochen Gai, Xiaochun Yu
RAD51-associated protein 1 (RAD51AP1) is known to promote homologous recombination (HR) repair. However, the precise mechanism of RAD51AP1 in HR repair is unclear. Here, we identify that RAD51AP1 associates with pre-rRNA. Both the N terminus and C terminus of RAD51AP1 recognize pre-rRNA. Pre-rRNA not only colocalizes with RAD51AP1 at double-strand breaks (DSBs) but also facilitates the recruitment
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Extracellular lactate as an alternative energy source for retinal bipolar cells J. Biol. Chem. (IF 5.5) Pub Date : 2024-02-24 Victor Calbiague Garcia, Yiyi Chen, Bárbara Cádiz, Felipe Tapia, François Paquet-Durand, Oliver Schmachtenberg
Retinal bipolar and amacrine cells receive visual information from photoreceptors and participate in the first steps of image processing in the retina. Several studies have suggested the operation of aerobic glycolysis and a lactate shuttle system in the retina due to the high production of this metabolite under aerobic conditions. However, whether bipolar cells form part of this metabolic circuit
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5-Methylcytosine transferase NSUN2 drives NRF2-mediated ferroptosis resistance in non-small cell lung cancer J. Biol. Chem. (IF 5.5) Pub Date : 2024-02-24 Youming Chen, Zuli Jiang, Chenxing Zhang, Lindong Zhang, Huanxiang Chen, Nan Xiao, Lu Bai, Hongyang Liu, Junhu Wan
RNA 5-methylcytosine (m5C) is an abundant chemical modification in mammalian RNAs and plays crucial roles in regulating vital physiological and pathological processes, especially in cancer. However, the dysregulation of m5C and its underlying mechanisms in non-small cell lung cancer (NSCLC) remain unclear. Here we identified that NSUN2, a key RNA m5C methyltransferase, is highly expressed in NSCLC
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A vertebrate Vangl2 translational variant required for planar cell polarity J. Biol. Chem. (IF 5.5) Pub Date : 2024-02-24 Alexandra Walton, Virginie Thomé, Diego Revinski, Sylvie Marchetto, Tania M. Puvirajesinghe, Stéphane Audebert, Luc Camoin, Eric Bailly, Laurent Kodjabachian, Jean-Paul Borg
First described in the milkweed bug , planar cell polarity (PCP) is a developmental process essential for embryogenesis and development of polarized structures in Metazoans. This signaling pathway involves a set of evolutionarily conserved genes encoding transmembrane (Vangl, Frizzled, Celsr) and cytoplasmic (Prickle, Dishevelled) molecules. Vangl2 is of major importance in embryonic development as
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The bacterial division protein MinDE has an independent function in flagellation J. Biol. Chem. (IF 5.5) Pub Date : 2024-02-23 Pinkilata Pradhan, Ashoka Chary Taviti, Tushar Kant Beuria
Before preparing for division, bacteria stop their motility. During the exponential growth phase in , when the rate of bacterial division is highest, the expression of flagellar genes is repressed and bacterial adhesion is enhanced. Hence, it is evident that cell division and motility in bacteria are linked; however, the specific molecular mechanism by which these two processes are linked is not known
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Epigenetic marks or not? The discovery of novel DNA modifications in eukaryotes J. Biol. Chem. (IF 5.5) Pub Date : 2024-02-23 Wei-Ying Meng, Zi-Xin Wang, Yunfang Zhang, Yujun Hou, Jian-Huang Xue
DNA modifications add another layer of complexity to the eukaryotic genome to regulate gene expression, playing critical roles as epigenetic marks. In eukaryotes, the study of DNA epigenetic modifications has been confined to 5mC and its derivatives for decades. However, rapid developing approaches have witnessed the expansion of DNA modification reservoirs during the past several years, including
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5-Formylcytosine mediated DNA-peptide cross-link induces predominantly semi-targeted mutations in both Escherichia coli and human cells J. Biol. Chem. (IF 5.5) Pub Date : 2024-02-23 Jan Henric T. Bacurio, Priscilla Yawson, Jenna Thomforde, Qi Zhang, Honnaiah Vijay Kumar, Holly Den Hartog, Natalia Y. Tretyakova, Ashis K. Basu
Histone proteins can become trapped on DNA in the presence of 5-formylcytosine (5fC) to form toxic DNA-protein conjugates. Their repair may involve proteolytic digestion resulting in DNA-peptide cross-links (DpCs). Here, we have investigated replication of a model DpC comprised of an 11-mer peptide (NH–GGGKGLG∗GGA) containing an oxy-lysine residue () conjugated to 5fC in DNA. Both CXG and CXT (where
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The small molecule activator S3969 stimulates the epithelial sodium channel by interacting with a specific binding pocket in the channel's β-subunit J. Biol. Chem. (IF 5.5) Pub Date : 2024-02-23 Florian Sure, Jürgen Einsiedel, Peter Gmeiner, Patrick Duchstein, Dirk Zahn, Christoph Korbmacher, Alexandr V. Ilyaskin
The epithelial sodium channel (ENaC) is essential for mediating sodium absorption in several epithelia. Its impaired function leads to severe disorders, including pseudohypoaldosteronism type 1 and respiratory distress. Therefore, pharmacological ENaC activators have potential therapeutic implications. Previously, a small molecule ENaC activator (S3969) was developed. So far, little is known about
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Triple-fusion protein (TRIFU): A potent, targeted, enzyme-like inhibitor of all three complement activation pathways J. Biol. Chem. (IF 5.5) Pub Date : 2024-02-23 Sophia J. Sonnentag, Arthur Dopler, Katharina Kleiner, Brijesh K. Garg, Marco Mannes, Nadja Späth, Amira Akilah, Britta Höchsmann, Hubert Schrezenmeier, Markus Anliker, Ruby Boyanapalli, Markus Huber-Lang, Christoph Q. Schmidt
The introduction of a therapeutic anti-C5 antibody into clinical practice in 2007 inspired a surge into the development of complement-targeted therapies. This has led to the recent approval of a C3 inhibitory peptide, an antibody directed against C1s and a full pipeline of several complement inhibitors in preclinical and clinical development. However, no inhibitor is available that efficiently inhibits
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Analysis of Poly(ethylene terephthalate) degradation kinetics of evolved IsPETase variants using a surface crowding model J. Biol. Chem. (IF 5.5) Pub Date : 2024-02-22 En Ze Linda Zhong-Johnson, Ziyue Dong, Christopher T. Canova, Francesco Destro, Marina Cañellas, Mikaila C. Hoffman, Jeanne Maréchal, Timothy M. Johnson, Gabriela S. Schlau-Cohen, Maria Fátima Lucas, Richard D. Braatz, Kayla G. Sprenger, Christopher A. Voigt, Anthony J. Sinskey
Poly(ethylene terephthalate) (PET) is a major plastic polymer utilized in the single-use and textile industries. The discovery of PET-degrading enzymes (PETases) has led to an increased interest in the biological recycling of PET in addition to mechanical recycling. PETase from is a candidate catalyst, but little is understood about its structure-function relationships with regards to PET degradation
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Functional domains of a ribosome arresting peptide are affected by surrounding nonconserved residues J. Biol. Chem. (IF 5.5) Pub Date : 2024-02-22 Heather N.G. Judd, Allyson K. Martínez, Dorota Klepacki, Nora Vázquez-Laslop, Matthew S. Sachs, Luis R. Cruz-Vera
Expression of the operon, responsible for L-tryptophan (L-Trp) transport and catabolism, is regulated by L-Trp–directed translation arrest and the ribosome arresting peptide TnaC. The function of TnaC relies on conserved residues distributed throughout the peptide, which are involved in forming an L-Trp binding site at the ribosome exit tunnel and inhibiting the ribosome function. We aimed to understand
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Unraveling the mystery of ocular retinoid turnover: Insights from albino mice and the role of STRA6 J. Biol. Chem. (IF 5.5) Pub Date : 2024-02-21 Srinivasagan Ramkumar, Beata Jastrzebska, Diego Montenegro, Janet R. Sparrow, Johannes von Lintig
A delicate balance between photon absorption for vision and the protection of photoreceptors from light damage is pivotal for ocular health. This equilibrium is governed by the light-absorbing 11--retinylidene chromophore of visual pigments, which, upon bleaching, transforms into all--retinal and undergoes regeneration through an enzymatic pathway, named the visual cycle. Chemical side reactions of
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SUMO modifies GβL and mediates mTOR signaling J. Biol. Chem. (IF 5.5) Pub Date : 2024-02-21 Sophia Louise Lucille Park, Uri Nimrod Ramírez-Jarquín, Neelam Shahani, Oscar Rivera, Manish Sharma, Preksha Sandipkumar Joshi, Aayushi Hansalia, Sunayana Dagar, Francis P. McManus, Pierre Thibault, Srinivasa Subramaniam
The mechanistic target of rapamycin (mTOR) signaling is influenced by multiple regulatory proteins and post-translational modifications; however, underlying mechanisms remain unclear. Here, we report a novel role of small ubiquitin–like modifier (SUMO) in mTOR complex assembly and activity. By investigating the SUMOylation status of core mTOR components, we observed that the regulatory subunit, GβL
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Munc18c accelerates SNARE-dependent membrane fusion in the presence of regulatory proteins α-SNAP and NSF J. Biol. Chem. (IF 5.5) Pub Date : 2024-02-21 Furong Liu, Ruyue He, Xinyu Xu, Min Zhu, Haijia Yu, Yinghui Liu
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SADS-CoV nsp1 inhibits the STAT1 phosphorylation by promoting K11/K48-linked polyubiquitination of JAK1 and blocks the STAT1 acetylation by degrading CBP J. Biol. Chem. (IF 5.5) Pub Date : 2024-02-21 Yingjie Xiang, Chunxiao Mou, Liqi Zhu, Ziyan Wang, Kaichuang Shi, Wenbin Bao, Jiarui Li, Xiang Chen, Zhenhai Chen
The newly discovered zoonotic coronavirus swine acute diarrhea syndrome coronavirus (SADS-CoV) causes acute diarrhea, vomiting, dehydration, and high mortality rates in newborn piglets. Although SADS-CoV uses different strategies to evade the host’s innate immune system, the specific mechanism(s) by which it blocks the interferon (IFN) response remains unidentified. In this study, the potential of
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Improved resolution of 3-mercaptopropionate dioxygenase active site provided by ENDOR spectroscopy offers insight into catalytic mechanism J. Biol. Chem. (IF 5.5) Pub Date : 2024-02-21 Brad S. Pierce, Allison N. Schmittou, Nicholas J. York, Ryan P. Madigan, Paula F. Nino, Frank W. Foss, Molly M. Lockart
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Identification of a conserved α-helical domain at the N terminus of human DNA methyltransferase 1 J. Biol. Chem. (IF 5.5) Pub Date : 2024-02-19 Qi Hu, Maria Victoria Botuyan, Georges Mer
In vertebrates, DNA methyltransferase 1 (DNMT1) contributes to preserving DNA methylation patterns, ensuring the stability and heritability of epigenetic marks important for gene expression regulation and the maintenance of cellular identity. Previous structural studies have elucidated the catalytic mechanism of DNMT1 and its specific recognition of hemimethylated DNA. Here, using solution nuclear
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ZNF692 regulates nucleolar morphology by interacting with NPM1 and modifying its self-assembly properties J. Biol. Chem. (IF 5.5) Pub Date : 2024-02-19 Isabella N. Brown, Arlene Levario, Chunhui Jiang, Weronika Stachera, Enrique Rodriguez, Yi-Heng Hao, Jeffrey B. Woodruff, M.Carmen Lafita-Navarro, Maralice Conacci-Sorrell
The nucleolus, a membraneless organelle, is responsible for ribosomal RNA transcription, ribosomal RNA processing, and ribosome assembly. Nucleolar size and number are indicative of a cell's protein synthesis rate and proliferative capacity, and abnormalities in the nucleolus have been linked to neurodegenerative diseases and cancer. In this study, we demonstrated that the nucleolar protein ZNF692
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Charge neutralization and β-elimination cleavage mechanism of family 42 L-rhamnose-α-1,4-D-glucuronate lyase revealed using neutron crystallography J. Biol. Chem. (IF 5.5) Pub Date : 2024-02-19 Naomine Yano, Tatsuya Kondo, Katsuhiro Kusaka, Takatoshi Arakawa, Tatsuji Sakamoto, Shinya Fushinobu
Gum arabic (GA) is widely used as an emulsion stabilizer and edible coating and consists of a complex carbohydrate moiety with a rhamnosyl-glucuronate group capping the non-reducing ends. Enzymes that can specifically cleave the glycosidic chains of GA and modify their properties are valuable for structural analysis and industrial application. Cryogenic X-ray crystal structure of GA-specific -rhamnose-α-1
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The splicing factor Prpf31 is required for hematopoietic stem and progenitor cell expansion during zebrafish embryogenesis J. Biol. Chem. (IF 5.5) Pub Date : 2024-02-19 Yuexia Lv, Jingzhen Li, Shanshan Yu, Yangjun Zhang, Hualei Hu, Kui Sun, Danna Jia, Yunqiao Han, Jiayi Tu, Yuwen Huang, Xiliang Liu, Xianghan Zhang, Pan Gao, Xiang Chen, Mark Thomas Shaw Williams, Zhaohui Tang, Xinhua Shu, Mugen Liu, Xiang Ren
Pre-mRNA splicing is a precise regulated process, and is crucial for system development and homeostasis maintenance. Mutations in spliceosomal components have been found in various hematopoietic malignancies (HMs), and have been considered as oncogenic derivers of HMs. However, the role of spliceosomal components in normal and malignant hematopoiesis remain largely unknown. Pre-mRNA processing factor
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Regulation of Calcium entry by cyclic GMP signaling in Toxoplasma gondii J. Biol. Chem. (IF 5.5) Pub Date : 2024-02-19 Miryam A. Hortua Triana, Karla M. Márquez-Nogueras, Mojtaba Sedigh Fazli, Shannon Quinn, Silvia N.J. Moreno
Ca signaling impacts almost every aspect of cellular life. Ca signals are generated through the opening of ion channels that permit the flow of Ca down an electrochemical gradient. Cytosolic Ca fluctuations can be generated through Ca entry from the extracellular milieu or release from intracellular stores. In Ca ions play critical roles in several essential functions for the parasite like invasion
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Withdrawal: Carbon monoxide protects against hyperoxia-induced endothelial cell apoptosis by inhibiting reactive oxygen species formation J. Biol. Chem. (IF 5.5) Pub Date : 2024-02-19 Xue Wang, Yong Wang, Hong Pyo Kim, Kiichi Nakahira, Stefan W. Ryter, Augustine M.K. Choi
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Structural basis for specific DNA sequence recognition by the transcription factor NFIL3 J. Biol. Chem. (IF 5.5) Pub Date : 2024-02-19 Sizhuo Chen, Ming Lei, Ke Liu, Jinrong Min
The CCAAT/enhancer-binding proteins (C/EBPs) constitute a family of pivotal transcription factors involved in tissue development, cellular function, proliferation, and differentiation. NFIL3, as one of them, plays an important role in regulating immune cell differentiation, circadian clock system, and neural regeneration, yet its specific DNA recognition mechanism remains enigmatic. In this study,
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Differential responses to UCP1 ablation in classical brown versus beige fat, despite a parallel increase in sympathetic innervation J. Biol. Chem. (IF 5.5) Pub Date : 2024-02-16 Qimuge Naren, Erik Lindsund, Muhammad Hamza Bokhari, Weijun Pang, Natasa Petrovic
In the cold, the absence of the mitochondrial uncoupling protein 1 (UCP1) results in hyper-recruitment of beige fat, but classical brown fat becomes atrophied. Here we examine possible mechanisms underlying this phenomenon. We confirm that in brown fat from UCP1-knockout (UCP1-KO) mice acclimated to the cold, the levels of mitochondrial respiratory chain proteins were diminished; however, in beige
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Compartmentalization of galactan biosynthesis in mycobacteria J. Biol. Chem. (IF 5.5) Pub Date : 2024-02-16 Karin Savková, Maksym Danchenko, Viktória Fabianová, Jana Bellová, Mária Bencúrová, Stanislav Huszár, Jana Korduláková, Barbara Siváková, Peter Baráth, Katarína Mikušová
Galactan polymer is a prominent component of the mycobacterial cell wall core. Its biogenesis starts at the cytoplasmic side of the plasma membrane by a build-up of the linker disaccharide [rhamnosyl (Rha) – N-acetyl-glucosaminyl (GlcNAc) phosphate] on the decaprenyl-phosphate carrier. This decaprenyl-P-P-GlcNAc-Rha intermediate is extended by two bifunctional galactosyl transferases, GlfT1 and GlfT2
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LncRNA CHROMR/miR-27b-3p/MET axis promotes the proliferation, invasion, and contributes to rituximab resistance in diffuse large B-cell lymphoma J. Biol. Chem. (IF 5.5) Pub Date : 2024-02-16 Chang Liu, Xinan Zhao, Zifeng Wang, Chan Zhang, Wenbin Zheng, Xiaoxia Zhu, Dong Zhang, Tao Gong, Hong Zhao, Feng Li, Tao Guan, Xiangyang Guo, Hongwei Zhang, Baofeng Yu
Long non-coding RNAs (LncRNAs) could regulate chemoresistance through sponging microRNAs (miRNAs) and sequestering RNA binding proteins. However, the mechanism of lncRNAs in rituximab resistance in diffuse large B-cell lymphoma (DLBCL) is largely unknown. Here, we investigated the functions and molecular mechanisms of lncRNA CHROMR in DLBCL tumorigenesis and chemoresistance. LncRNA CHROMR is highly
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Extracellular domain mutations of the EGF receptor differentially modulate high-affinity and low-affinity responses to EGF receptor ligands J. Biol. Chem. (IF 5.5) Pub Date : 2024-02-16 Jennifer L. Macdonald-Obermann, Linda J. Pike
The EGF receptor is mutated in a number of cancers. In most cases, the mutations occur in the intracellular tyrosine kinase domain. However, in glioblastomas, many of the mutations are in the extracellular ligand binding domain. To determine what changes in receptor function are induced by such extracellular domain mutations, we analyzed the binding and biological response to the seven different EGF
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Mechanistic insights into the C-type lectin receptor CLEC12A-mediated immune recognition of monosodium urate crystal J. Biol. Chem. (IF 5.5) Pub Date : 2024-02-16 Hua Tang, Yuelong Xiao, Lei Qian, Zibin Wang, Ming Lu, Nan Yao, Ting Zhou, Fang Tian, Longxing Cao, Peng Zheng, Xianchi Dong
CLEC12A, a member of the C-type lectin receptor family involved in immune homeostasis, recognizes MSU crystals released from dying cells. However, the molecular mechanism underlying the CLEC12A-mediated recognition of MSU crystals still remains unclear. Herein, we reported the crystal structure of the human CLEC12A-CTLD and identified a unique “basic patch” site on CLEC12A-CTLD that is necessary for
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CHEK2 germline variants identified in familial non-medullary thyroid cancer lead to impaired protein structure and function J. Biol. Chem. (IF 5.5) Pub Date : 2024-02-16 Carolina Pires, Inês J. Marques, Mariana Valério, Ana Saramago, Paulo E. Santo, Sandra Santos, Margarida Silva, Margarida M. Moura, João Matos, Teresa Pereira, Rafael Cabrera, Diana Lousa, Valeriano Leite, Tiago M. Bandeiras, João B. Vicente, Branca M. Cavaco
Approximately 5-15% of non-medullary thyroid cancers (NMTC) present in a familial form (FNMTC). Unlike sporadic NMTC, the genetic basis of FNMTC remains largely unknown, representing a limitation for diagnostic, therapeutic and follow-up decisions. Recently, germline mutations in DNA repair-related genes have been described in cases with thyroid cancer, suggesting a role in FNMTC etiology. Here, two
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Both Las17-binding sites on Arp2/3 complex are important for branching nucleation and assembly of functional endocytic actin networks in S. cerevisiae J. Biol. Chem. (IF 5.5) Pub Date : 2024-02-16 Heidy Y. Narvaez-Ortiz, Michael J. Lynch, Su-Ling Liu, Adam Fries, Brad J. Nolen
Arp2/3 complex nucleates branched actin filaments that drive membrane invagination during endocytosis and leading-edge protrusion in lamellipodia. Arp2/3 complex is maximally activated by binding of a WASP family protein to two sites—one on the Arp3 subunit and one spanning Arp2 and ARPC1—but the importance of each site in the regulation of force-producing actin networks is unclear. Here, we identify
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The RsfSR two-component system regulates SigF function by monitoring the state of the respiratory electron transport chain in Mycobacterium smegmatis J. Biol. Chem. (IF 5.5) Pub Date : 2024-02-16 Yuna Oh, Jeong-Il Oh
In , the transcriptional activity of the alternative sigma factor SigF is posttranslationally regulated by the partner switching system consisting of SigF, the anti-SigF RsbW1, and three anti-SigF antagonists (RsfA, RsfB, and RsbW3). We previously demonstrated that expression of the SigF regulon is strongly induced in the Δ mutant of lacking the cytochrome oxidase, the major terminal oxidase in the
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Heterotrimeric G protein signaling without GPCRs: The Gα-binding-and-activating motif J. Biol. Chem. (IF 5.5) Pub Date : 2024-02-15 Mikel Garcia-Marcos
Heterotrimeric G proteins (Gαβγ) are molecular switches that relay signals from 7-transmembrane receptors located at the cell surface to the cytoplasm. The function of these receptors is so intimately linked to heterotrimeric G proteins that they are named G protein–coupled receptors (GPCRs), showcasing the interdependent nature of this archetypical receptor–transducer axis of transmembrane signaling