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The Multifaceted Role of Intracellular Glycosylation in Cytoprotection and Heart Disease J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-18 Priya Umapathi, Akanksha Aggarwal, Fiddia Zahra, Bhargavi Narayanan, Natasha E. Zachara
The modification of nuclear, cytoplasmic, and mitochondrial proteins by O-linked β-N-acetylglucosamine (O-GlcNAc) is an essential post-translational modification common in metazoans. O-GlcNAc is cycled on and off proteins in response to environmental and physiological stimuli impacting protein function, which, in turn, tunes pathways that include transcription, translation, proteostasis, signal transduction
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Hypothiocyanous acid reductase is critical for host colonization and infection by Streptococcus pneumoniae J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-09 Heather L. Shearer, Michael J. Currie, Hannah N. Agnew, Claudia Trappetti, Frederick Stull, Paul E. Pace, James C. Paton, Renwick C.J. Dobson, Nina Dickerhof
The major human pathogen encounters the immune-derived oxidant hypothiocyanous acid (HOSCN) at sites of colonization and infection. We recently identified the pneumococcal hypothiocyanous acid reductase (Har), a member of the flavoprotein disulfide reductase enzyme family, and showed that it contributes to the HOSCN tolerance of . Here, we demonstrate in mouse models of pneumococcal infection that
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A novel system to determine activity of individual uridine 5′-diphospho-glucuronosyltransferase (UGT) isoforms: Recombinant UGT-beads J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-08 Ting Wang, Mitchell E. Taub, Tom S. Chan
Previous work demonstrated that human liver microsomes (HLMs) can spontaneously bind to silica-coated magnetizable beads (HLM-beads) and that these HLM-beads retain uridine 5′-diphospho-glucuronosyltransferase (UGT) activity. However, the contributions of individual UGT isoforms are not directly assessable in this system except through use of model inhibitors. Thus, a preparation wherein recombinant
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TFE3–SLC36A1 axis promotes resistance to glucose starvation in kidney cancer cells J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-08 Suli Lv, Zongbiao Zhang, Zhenyong Li, Qian Ke, Xianyun Ma, Neng Li, Xuefeng Zhao, Qingli Zou, Lidong Sun, Tanjing Song
Higher demand for nutrients including glucose is characteristic of cancer. "Starving cancer" has been pursued to curb tumor progression. An intriguing regime is to inhibit glucose transporter GLUT1 in cancer cells. In addition, during cancer progression, cancer cells may suffer from insufficient glucose supply. Yet, cancer cells can somehow tolerate glucose starvation. Uncovering the underlying mechanisms
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Ancestral sequence reconstruction dissects structural and functional differences among eosinophil ribonucleases J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-07 Thi Thanh Quynh Tran, Chitra Narayanan, Andrea N. Loes, Timothy H. Click, N.T.Hang Pham, Myriam Létourneau, Michael J. Harms, Charles Calmettes, Pratul K. Agarwal, Nicolas Doucet
Evolutionarily conserved structural folds can give rise to diverse biological functions, yet predicting atomic-scale interactions that contribute to the emergence of novel activities within such folds remains challenging. Pancreatic-type ribonucleases illustrate this complexity, sharing a core structure that has evolved to accommodate varied functions. In this study, we used ancestral sequence reconstruction
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Mitotic spindle positioning protein (MISP) preferentially binds to aged F-actin J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-07 E. Angelo Morales, Gillian N. Fitz, Matthew J. Tyska
Actin bundling proteins crosslink filaments into polarized structures that shape and support membrane protrusions including filopodia, microvilli, and stereocilia. In the case of epithelial microvilli, mitotic spindle positioning protein (MISP) is an actin bundler that localizes specifically to the basal rootlets, where the pointed ends of core bundle filaments converge. Previous studies established
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Spatial organization of bacterial sphingolipid synthesis enzymes J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-07 Chioma G. Uchendu, Ziqiang Guan, Eric A. Klein
Sphingolipids are produced by nearly all eukaryotes where they play significant roles in cellular processes such as cell growth, division, programmed cell death, angiogenesis, and inflammation. While it was previously believed that sphingolipids were quite rare among bacteria, bioinformatic analysis of the recently identified bacterial sphingolipid synthesis genes suggests that these lipids are likely
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Impaired malin expression and interaction with partner proteins in Lafora disease J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-07 Alexander V. Skurat, Dyann M. Segvich, Christopher J. Contreras, Yueh-Chiang Hu, Thomas D. Hurley, Anna A. DePaoli-Roach, Peter J. Roach
Lafora disease (LD) is an autosomal recessive myoclonus epilepsy with onset in the teenage years leading to death within a decade of onset. LD is characterized by the overaccumulation of hyperphosphorylated, poorly branched, insoluble, glycogen-like polymers called Lafora bodies. The disease is caused by mutations in either , encoding laforin, a dual specificity phosphatase that dephosphorylates glycogen
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Functional identification of bacterial spermine, thermospermine, norspermine, norspermidine, spermidine, and N1-aminopropylagmatine synthases J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-06 Bin Li, Jue Liang, Hamid R. Baniasadi, Shin Kurihara, Margaret A. Phillips, Anthony J. Michael
Spermine synthase is an aminopropyltransferase that adds an aminopropyl group to the essential polyamine spermidine to form tetraamine spermine, needed for normal human neural development, plant salt and drought resistance, and yeast CoA biosynthesis. We functionally identify for the first time bacterial spermine synthases, derived from phyla Bacillota, Rhodothermota, Thermodesulfobacteriota, Nitrospirota
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The luciferase-based in vivo protein–protein interaction assay revealed that CHK1 promotes PP2A and PME-1 interaction J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-06 Sana Ando, Keiko Tanaka, Maharu Matsumoto, Yuki Oyama, Yuri Tomabechi, Atsushi Yamagata, Mikako Shirouzu, Reiko Nakagawa, Noriaki Okimoto, Makoto Taiji, Koichi Sato, Takashi Ohama
Protein phosphatase 2A (PP2A) is an essential serine/threonine protein phosphatase, and its dysfunction is involved in the onset of cancer and neurodegenerative disorders. PP2A functions as a trimeric holoenzyme whose composition is regulated by the methyl-esterification (methylation) of the PP2A catalytic subunit (PP2Ac). Protein phosphatase methylesterase-1 (PME-1) is the sole PP2Ac methylesterase
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Biochemical characterization of Escherichia coli DnaC variants that alter DnaB helicase loading onto DNA J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-06 Sarah D. McMillan, James L. Keck
DNA replication in starts with the loading of the replicative helicase, DnaB, onto DNA. This reaction requires the DnaC loader protein, which forms a 6:6 complex with DnaB and opens a channel in the DnaB hexamer through which single-stranded DNA is thought to pass. During replication, replisomes frequently encounter DNA damage and nucleoprotein complexes that can lead to replication fork collapse.
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Ykt6 functionally overlaps with vacuolar and exocytic R-SNAREs in the yeast Saccharomyces cerevisiae J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-06 Hayate Watanabe, Shingo Urano, Nozomi Kikuchi, Yurika Kubo, Ayumi Kikuchi, Katsuya Gomi, Takahiro Shintani
The soluble -ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex forms a 4-helix coiled-coil bundle consisting of 16 layers of interacting side chains upon membrane fusion. The central layer (layer 0) is highly conserved and comprises three glutamines (Q) and one arginine (R), and thus SNAREs are classified into Qa-, Qb-, Qc-, and R-SNAREs. Homotypic vacuolar fusion in requires
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ARV1 deficiency induces lipid bilayer stress and enhances rDNA stability by activating the unfolded protein response in Saccharomyces cerevisiae J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-06 Sujin Hong, Hyeon-geun Lee, Won-Ki Huh
The stability of ribosomal DNA (rDNA) is maintained through transcriptional silencing by the NAD-dependent histone deacetylase Sir2 in . Alongside proteostasis, rDNA stability is a crucial factor regulating the replicative lifespan of . The unfolded protein response (UPR) is induced by misfolding of proteins or an imbalance of membrane lipid composition and is responsible for degrading misfolded proteins
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Immunometabolic crosstalk in Aedes fluviatilis Wolbachia pipientis symbiosis J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-06 Jhenifer Nascimento da Silva, Christiano Calixto Conceição, Gisely Cristina Ramos de Brito, Carlos Renato de Oliveira Daumas Filho, Ana Beatriz Walter Nuno, Octavio A.C. Talyuli, Angélica Arcanjo, Pedro L. de Oliveira, Luciano Andrade Moreira, Itabajara da Silva Vaz Jr, Carlos Logullo
is a maternally transmitted symbiotic bacterium that mainly colonizes arthropods, potentially affecting different aspects of the host's physiology, , reproduction, immunity, and metabolism. It has been shown that Wolbachia modulates glycogen metabolism in mosquito (). Glycogen synthesis is controlled by the enzyme GSK3, which is also involved in immune responses in both vertebrate and invertebrate
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Coenzyme Q4 is a functional substitute for coenzyme Q10 and can be targeted to the mitochondria J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-06 Laura H. Steenberge, Sean Rogers, Andrew Y. Sung, Jing Fan, David J. Pagliarini
Coenzyme Q10 (CoQ) is an important cofactor and antioxidant for numerous cellular processes, and its deficiency has been linked to human disorders including mitochondrial disease, heart failure, Parkinson’s disease, and hypertension. Unfortunately, treatment with exogenous CoQ is often ineffective, likely due to the extreme hydrophobicity and high molecular weight of CoQ. Here, we show that less hydrophobic
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Phospholamban inhibits the cardiac calcium pump by interrupting an allosteric activation pathway J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-06 Sean R. Cleary, Jaroslava Seflova, Ellen E. Cho, Konark Bisht, Himanshu Khandelia, L. Michel Espinoza-Fonseca, Seth L. Robia
Phospholamban (PLB) is a transmembrane micropeptide that regulates the sarcoplasmic reticulum Ca-ATPase (SERCA) in cardiac muscle, but the physical mechanism of this regulation remains poorly understood. PLB reduces the Ca sensitivity of active SERCA, increasing the Ca concentration required for pump cycling. However, PLB does not decrease Ca binding to SERCA when ATP is absent, suggesting PLB does
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Pathogenic residue insertion in a neuronal nicotinic receptor alters intrasubunit and intersubunit interactions that tune channel gating J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-06 Deborah J. Msekela, Steven M. Sine
We describe molecular-level functional changes in the α4β2 nicotinic acetylcholine receptor by a leucine residue insertion in the M2 transmembrane domain of the α4 subunit associated with sleep-related hyperkinetic epilepsy. Measurements of agonist-elicited single-channel currents reveal the primary effect is to stabilize the open channel state, while the secondary effect is to promote reopening of
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Structural characterization of methylation-independent PP2A assembly guides alphafold2Multimer prediction of family-wide PP2A complexes J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-04 Franziska Wachter, Radosław P. Nowak, Scott Ficarro, Jarrod Marto, Eric S. Fischer
Dysregulation of phosphorylation-dependent signaling is a hallmark of tumorigenesis. Protein phosphatase 2 (PP2A) is an essential regulator of cell growth. One scaffold subunit (A) binds to a catalytic subunit (C) to form a core AC heterodimer, which together with one of many regulatory (B) subunits forms the active trimeric enzyme. The combinatorial number of distinct PP2A complexes is large, which
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The sensor of the bacterial histidine kinase CpxA is a novel dimer of extracytoplasmic Per-ARNT-Sim domains J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-04 Timothy H.S. Cho, Cameron Murray, Roxana Malpica, Rodrigo Margain-Quevedo, Gina L. Thede, Jun Lu, Ross A. Edwards, J.N.Mark Glover, Tracy L. Raivio
Histidine kinases are key bacterial sensors that recognize diverse environmental stimuli. While mechanisms of phosphorylation and phosphotransfer by cytoplasmic kinase domains are relatively well-characterized, the ways in which extracytoplasmic sensor domains regulate activation remain mysterious. The Cpx envelope stress response is a conserved Gram-negative two-component system which is controlled
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Applications of protein ubiquitylation and deubiquitylation in drug discovery J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-04 Yilin Chen, Haoan Xue, Jianping Jin
The ubiquitin (Ub)–proteasome system (UPS) is the major machinery mediating specific protein turnover in eukaryotic cells. By ubiquitylating unwanted, damaged, or harmful proteins and driving their degradation, UPS is involved in many important cellular processes. Several new UPS-based technologies, including molecular glue degraders and PROTACs (proteolysis-targeting chimeras) to promote protein degradation
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JNK activity modulates postsynaptic scaffold protein SAP102 and kainate receptor dynamics in dendritic spines J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-04 Stella-Amrei Kunde, Bettina Schmerl, Judith von Sivers, Elham Ahmadyar, Taanisha Gupta, Nils Rademacher, Hanna L. Zieger, Sarah A. Shoichet
Synapse formation depends on the coordinated expression and regulation of scaffold proteins. The JNK family kinases play a role in scaffold protein regulation, but the nature of this functional interaction in dendritic spines requires further investigation. Here, using a combination of biochemical methods and live-cell imaging strategies, we show that the dynamics of the synaptic scaffold molecule
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The molecular principles underlying diverse functions of the SLC26 family of proteins J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-04 Satoe Takahashi, Kazuaki Homma
Mammalian SLC26 proteins are membrane-based anion transporters that belong to the large SLC26/SulP family, and many of their variants are associated with hereditary diseases. Recent structural studies revealed a strikingly similar homodimeric molecular architecture for several SLC26 members, implying a shared molecular principle. Now a new question emerges as to how these structurally similar proteins
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KLF15 maintains contractile phenotype of vascular smooth muscle cells and prevents thoracic aortic dissection by interacting with MRTFB J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-04 Guangming Fang, Yexuan Tian, Shan Huang, Xiaoping Zhang, Yan Liu, Yulin Li, Jie Du, Shijuan Gao
Thoracic aortic dissection (TAD) is a highly dangerous cardiovascular disorder caused by weakening of the aortic wall, resulting in a sudden tear of the internal face. Progressive loss of the contractile apparatus in vascular smooth muscle cells (VSMCs) is a major event in TAD. Exploring the endogenous regulators essential for the contractile phenotype of VSMCs may aid the development of strategies
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Selenoprotein I is indispensable for ether lipid homeostasis and proper myelination J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-04 Lance G.A. Nunes, Chi Ma, FuKun W. Hoffmann, Ashley E. Shay, Matthew W. Pitts, Peter R. Hoffmann
Selenoprotein I (SELENOI) catalyzes the final reaction of the CDP-ethanolamine branch of the Kennedy pathway, generating the phospholipids phosphatidylethanolamine (PE) and plasmenyl-PE. Plasmenyl-PE is a key component of myelin and is characterized by a vinyl ether bond that preferentially reacts with oxidants, thus serves as a sacrificial antioxidant. In humans, multiple loss-of-function mutations
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Structural analysis of the SAM domain of the Arabidopsis mitochondrial tRNA import receptor J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-04 Bence Olasz, Luke Smithers, Genevieve L. Evans, Anandhi Anandan, Monika W. Murcha, Alice Vrielink
Mitochondria are membrane-bound organelles of endosymbiotic origin with limited protein-coding capacity. The import of nuclear-encoded protein and nucleic acids is required and essential for maintaining organelle mass, number, and activity. As plant mitochondria do not encode all the necessary tRNA types required, the import of cytosolic tRNA is vital for organelle maintenance. Recently, two mitochondrial
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Making a living off the rainbow’s edge: How phycobilisomes adapt structurally to absorb far-red light J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-03 Matthew S. Kimber
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Mst4, a novel cardiac STRIPAK complex–associated kinase, regulates cardiomyocyte growth and survival and is upregulated in human cardiomyopathy J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-03 Matthias Eden, Marius Leye, Justus Hahn, Emanuel Heilein, Marcin Luzarowski, Bill Völschow, Christin Tannert, Samuel Sossalla, Carlota Lucena-Porcel, Derk Frank, Norbert Frey
Myocardial failure is associated with adverse remodeling, which includes apoptotic loss of cardiomyocytes, hypertrophy, as well as alterations in cell–cell contacts. Striatin-interacting phosphatase and kinase (STRIPAK) complexes and their kinase mammalian STE20-like kinase 4 (Mst4) have been linked to the development of different diseases. The role and targets of Mst4 in cardiomyocytes have not been
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Interplay of RAP2 GTPase and the cytoskeleton in Hippo pathway regulation J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-02 Chenzhou Wu, Xiaomin Cai, Ying Wang, Carlos D. Rodriguez, Giorgia Zoaldi, Lydia Herrmann, Chun-Yuh Huang, Xiaoqiong Wang, Viraj R. Sanghvi, Rongze O. Lu, Zhipeng Meng
The Hippo signaling is instrumental in regulating organ size, regeneration, and carcinogenesis. The cytoskeleton emerges as a primary Hippo signaling modulator. Its structural alterations in response to environmental and intrinsic stimuli control Hippo signaling pathway activity. However, the precise mechanisms underlying the cytoskeleton regulation of Hippo signaling are not fully understood. RAP2
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Receptor-activated transcription factors and beyond: multiple modes of Smad2/3-dependent transmission of TGF-β signaling J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-02 Keiji Miyazawa, Yuka Itoh, Hao Fu, Kohei Miyazono
Transforming growth factor β (TGF-β) is a pleiotropic cytokine that is widely distributed throughout the body. Its receptor proteins, TGF-β type I and type II receptors, are also ubiquitously expressed. Therefore, the regulation of various signaling outputs in a context-dependent manner is a critical issue in this field. Smad proteins were originally identified as signal-activated transcription factors
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Nesprin-2 is a novel scaffold protein for telethonin and FHL-2 in the cardiomyocyte sarcomere J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-02 Chen Li, Derek T. Warren, Can Zhou, Shanelle De Silva, Darren G.S. Wilson, Mitla Garcia-Maya, Mathew A. Wheeler, Peter Meinke, Greta Sawyer, Elisabeth Ehler, Manfred Wehnert, Li Rao, Qiuping Zhang, Catherine M. Shanahan
Nesprins comprise a family of multi-isomeric scaffolding proteins, forming the linker of nucleoskeleton-and-cytoskeleton complex with lamin A/C, emerin and SUN1/2 at the nuclear envelope. Mutations in nesprin-1/-2 are associated with Emery-Dreifuss muscular dystrophy (EDMD) with conduction defects and dilated cardiomyopathy (DCM). We have previously observed sarcomeric staining of nesprin-1/-2 in cardiac
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In silico prediction of heme binding in proteins J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-02 Noa A. Marson, Andrea E. Gallio, Suman K. Mandal, Roman A. Laskowski, Emma L. Raven
The process of heme binding to a protein is prevalent in almost all forms of life to control many important biological properties, such as O-binding, electron transfer, gas sensing or to build catalytic power. In these cases, heme typically binds tightly (irreversibly) to a protein in a discrete heme binding pocket, with one or two heme ligands provided most commonly to the heme iron by His, Cys or
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Structure-function analysis of plant G-protein regulatory mechanisms identifies key Gα-RGS protein interactions J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-01 Maria Daniela Torres-Rodriguez, Soon Goo Lee, Swarup Roy Choudhury, Rabindranath Paul, Balaji Selvam, Diwakar Shukla, Joseph M. Jez, Sona Pandey
Heterotrimeric GTP-binding protein alpha subunit (Gα) and its cognate regulator of G-protein signaling (RGS) protein transduce signals in eukaryotes spanning protists, amoeba, animals, fungi, and plants. The core catalytic mechanisms of the GTPase activity of Gα and the interaction interface with RGS for the acceleration of GTP hydrolysis seem to be conserved across these groups; however, the gene
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Engineered interleukin-6-derived cytokines recruit artificial receptor complexes and disclose CNTF signaling via the OSMR J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-01 Puyan Rafii, Patricia Rodrigues Cruz, Julia Ettich, Christiane Seibel, Giacomo Padrini, Christoph Wittich, Alexander Lang, Patrick Petzsch, Karl Köhrer, Jens M. Moll, Doreen M. Floss, Jürgen Scheller
Ciliary neurotrophic factor (CNTF) activates cells the non-signaling α-receptor CNTF receptor (CNTFR) and the two signaling β-receptors glycoprotein 130 (gp130) and leukemia inhibitory factor receptor (LIFR). The CNTF derivate, Axokine, was protective against obesity and insulin resistance, but clinical development was halted by the emergence of CNTF antibodies. The chimeric cytokine IC7 used the framework
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The IgG-specific endoglycosidases EndoS and EndoS2 are distinguished by conformation and antibody recognition J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-01 Abigail S.L. Sudol, Max Crispin, Ivo Tews
The IgG-specific endoglycosidases EndoS and EndoS2 from can remove conserved -linked glycans present on the Fc region of host antibodies to inhibit Fc-mediated effector functions. These enzymes are therefore being investigated as therapeutics for suppressing unwanted immune activation, and have additional application as tools for antibody glycan remodeling. EndoS and EndoS2 differ in Fc glycan substrate
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Human eukaryotic initiation factor 4G directly binds the 40S ribosomal subunit to promote efficient translation J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-01 Nancy Villa, Christopher S. Fraser
Messenger RNA (mRNA) recruitment to the 40S ribosomal subunit is mediated by eukaryotic initiation factor 4F (eIF4F). This complex includes three subunits: eIF4E (mG cap-binding protein), eIF4A (DEAD-box helicase), and eIF4G. Mammalian eIF4G is a scaffold that coordinates the activities of eIF4E and eIF4A and provides a bridge to connect the mRNA and 40S ribosomal subunit through its interaction with
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Homocysteine-induced sustained GluN2A NMDA receptor stimulation leads to mitochondrial ROS generation and neurotoxicity J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-01 Satya Narayan Deep, Sarah Seelig, Surojit Paul, Ranjana Poddar
Homocysteine, a sulfur-containing amino acid derived from methionine metabolism, is a known agonist of N-methyl-D-aspartate receptor (NMDAR) and is involved in neurotoxicity. Our previous findings showed that neuronal exposure to elevated homocysteine levels leads to sustained low-level increase in intracellular Ca, which is dependent on GluN2A subunit-containing NMDAR (GluN2A-NMDAR) stimulation. These
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Bacterial stigmasterol degradation involving radical flavin delta-24 desaturase and molybdenum-dependent C26 hydroxylase J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-30 Tingyi Zhan, Christian Jacoby, Martin Jede, Bettina Knapp, Sascha Ferlaino, Andreas Günter, Friedel Drepper, Michael Müller, Stefan Weber, Matthias Boll
Sterols are ubiquitous membrane constituents that persist to a large extent in the environment due to their water insolubility and chemical inertness. Recently, an oxygenase-independent sterol degradation pathway was discovered in a cholesterol-grown denitrifying bacterium (.) . It achieves hydroxylation of the unactivated primary C26 of the isoprenoid side chain to an allylic alcohol via a phosphorylated
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The immune checkpoint receptor LAG3: Structure, function, and target for cancer immunotherapy J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-30 Roy A. Mariuzza, Salman Shahid, Sharanbasappa S. Karade
Lymphocyte activation gene 3 protein (LAG3) is an immune checkpoint receptor that is highly upregulated on exhausted T cells in the tumor microenvironment. LAG3 transmits inhibitory signals to T cells upon binding to MHC class II and other ligands, rendering T cells dysfunctional. Consequently, LAG3 is a major target for cancer immunotherapy with many anti-LAG3 monoclonal antibodies (mAbs) that block
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Engineering a human P2X2 receptor with altered ligand selectivity in yeast J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-29 Elizabeth C. Gardner, Caitlin Tramont, Petra Bachanová, Chad Wang, Hannah Do, Daniel R. Boutz, Shaunak Kar, Boris V. Zemelman, Jimmy D. Gollihar, Andrew D. Ellington
P2X receptors are a family of ligand gated ion channels found in a range of eukaryotic species including humans but are not naturally present in the yeast . We demonstrate the first recombinant expression and functional gating of the P2X2 receptor in baker’s yeast. We leverage the yeast host for facile genetic screens of mutant P2X2 by performing site saturation mutagenesis at residues of interest
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Increased expression of long non-coding RNA FIRRE promotes hepatocellular carcinoma by HuR-CyclinD1 axis signaling J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-29 Yuki Haga, Debojyoty Bandyopadhyay, Mousumi Khatun, Ellen Tran, Robert Steele, Sumona Banerjee, Ranjit Ray, Mustafa Nazzal, Ratna B. Ray
There is a critical need to understand the disease processes and identify improved therapeutic strategies for hepatocellular carcinoma (HCC). The long noncoding RNAs (lncRNAs) display diverse effects on biological regulations. The aim of this study was to identify a lncRNA as a potential biomarker of HCC and investigate the mechanisms by which the lncRNA promotes HCC progression using human cell lines
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Blocking the dimerization of polyglutamine-expanded androgen receptors protects cells from DHT-induced toxicity by increasing AR turnover J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-29 Allison Lisberg, Yuhong Liu, Diane E. Merry
Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular degenerative disease caused by a polyglutamine expansion in the androgen receptor (AR). This mutation causes AR to misfold and aggregate, contributing to toxicity in and degeneration of motor neurons and skeletal muscle. There is currently no effective treatment or cure for this disease. The role of an interdomain interaction between the
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Tissue-specific transcriptional programming of macrophages controls the microRNA transcriptome targeting multiple functional pathways J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-29 Magdalena A. Czubala, Robert H. Jenkins, Mark Gurney, Leah Wallace, Benjamin Cossins, James Dennis, Marcela Rosas, Robert Andrews, Donald Fraser, Philip R. Taylor
Recent interest in the biology and function of peritoneal tissue resident macrophages (pMΦ) has led to a better understanding of their cellular origin, programming, and renewal. The programming of pMΦ is dependent on microenvironmental cues and tissue-specific transcription factors, including GATA6. However, the contribution of microRNAs remains poorly defined. We conducted a detailed analysis of the
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Key roles for phosphorylation and the coiled-coil domain in TRIM56-mediated positive regulation of TLR3-TRIF–dependent innate immunity J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-29 Benjamin M. Liu, Nan L. Li, Ruixue Wang, Xiaofan Li, Z. Alex Li, Tony N. Marion, Kui Li
Tripartite-motif protein-56 (TRIM56) positively regulates the induction of type I interferon response the TLR3 pathway by enhancing IRF3 activation and depends on its C-terminal residues 621 to 750 for interacting with the adaptor TRIF. However, the precise underlying mechanism and detailed TRIM56 determinants remain unclear. Herein, we show ectopic expression of murine TRIM56 also enhances TLR3-dependent
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The LOV-domain blue-light receptor LreA of the fungus Alternaria alternata binds predominantly FAD as chromophore and acts as a light and temperature sensor J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-28 Lars Schuhmacher, Steffen Heck, Michael Pitz, Elena Mathey, Tilman Lamparter, Alexander Blumhofer, Kai Leister, Reinhard Fischer
Light and temperature sensing are important features of many organisms. Light may provide energy but may also be used by non-photosynthetic organisms for orientation in the environment. Recent evidence suggests that plant and fungal phytochrome and plant phototropin serve dual functions as light and temperature sensors. Here we characterized the fungal LOV-domain blue-light receptor LreA of and show
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Tau regulates Arc stability in neuronal dendrites via a proteasome-sensitive but ubiquitin-independent pathway J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-27 Dina W. Yakout, Ankit Shroff, Wei Wei, Vishrut Thaker, Zachary D. Allen, Mathew Sajish, Taras Y. Nazarko, Angela M. Mabb
Tauopathies are neurodegenerative disorders characterized by the deposition of aggregates of the microtubule-associated protein tau, a main component of neurofibrillary tangles. Alzheimer’s disease (AD) is the most common type of tauopathy and dementia, with amyloid-beta pathology as an additional hallmark feature of the disease. Besides its role in stabilizing microtubules, tau is localized at postsynaptic
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The molecular determinants of classical pathway complement inhibition by OspEF-related proteins of Borrelia burgdorferi J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-27 Sheila Thomas, Anna M. Schulz, John M. Leong, Tonya N. Zeczycki, Brandon L. Garcia
The complement system serves as the first line of defense against invading pathogens by promoting opsonophagocytosis and bacteriolysis. Antibody-dependent activation of complement occurs through the classical pathway and relies on the activity of initiating complement proteases of the C1 complex, C1r and C1s. The causative agent of Lyme disease, , expresses two paralogous outer surface lipoproteins
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Deafness-associated tRNAPhe mutation impaired mitochondrial and cellular integrity J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-27 Xiaowan Chen, Feilong Meng, Chao Chen, Shujuan Li, Zhiqiang Chou, Baicheng Xu, Jun Q. Mo, Yufen Guo, Min-Xin Guan
Defects in mitochondrial RNA metabolism have been linked to sensorineural deafness that often occurs as a consequence of damaged or deficient inner ear hair cells. In this report, we investigated the molecular mechanism underlying a deafness-associated tRNA 593T > C mutation that changed a highly conserved uracil to cytosine at position 17 of the DHU-loop. The m.593T > C mutation altered tRNA structure
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Protein kinase A is a functional component of focal adhesions J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-27 Mingu Kang, Amanda J. Senatore, Hannah Naughton, Madeline McTigue, Rachel J. Beltman, Andrew A. Herppich, Mary Kay H. Pflum, Alan K. Howe
Focal adhesions (FAs) form the junction between extracellular matrix (ECM)-bound integrins and the actin cytoskeleton and also transmit signals that regulate cell adhesion, cytoskeletal dynamics, and cell migration. While many of these signals are rooted in reversible tyrosine phosphorylation, phosphorylation of FA proteins on Ser/Thr residues is far more abundant yet its mechanisms and consequences
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SLC25A3 negatively regulates NLRP3 inflammasome activation by restricting the function of NLRP3 J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-27 Feng Xiao, Yaling Jia, Simeng Zhang, Nanfang Liu, Xuelong Zhang, Tianci Wang, Jialu Qiao, Ge Yang, Xu Che, Keli Chen, Pan Pan, Lingli Zhou, Binlian Sun, Jun Chen, Pin Wan
The NACHT, leucine-rich repeat, and pyrin domains-containing protein 3 (collectively known as NLRP3) inflammasome activation plays a critical role in innate immune and pathogenic microorganism infections. However, excessive activation of NLRP3 inflammasome will lead to cellular inflammation and tissue damage, and naturally it must be precisely controlled in the host. Here, we discovered that solute
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The constitutively active form of a key cholesterol synthesis enzyme is lipid droplet-localized and upregulated in endometrial cancer tissues J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-26 Hudson W. Coates, Tina B. Nguyen, Ximing Du, Ellen M. Olzomer, Rhonda Farrell, Frances L. Byrne, Hongyuan Yang, Andrew J. Brown
Cholesterol is essential for both normal cell viability and cancer cell proliferation. Aberrant activity of squalene monooxygenase (SM, also known as squalene epoxidase), the rate-limiting enzyme of the committed cholesterol synthesis pathway, is accordingly implicated in a growing list of cancers. We previously reported that hypoxia triggers the truncation of SM to a constitutively active form, thus
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Mimicking kidney flow shear efficiently induces aggregation of LECT2, a protein involved in renal amyloidosis J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-26 Jeung-Hoi Ha, Yikang Xu, Harsimranjit Sekhon, Wenhan Zhao, Stephan Wilkens, Dacheng Ren, Stewart N. Loh
Aggregation of leukocyte cell-derived chemotaxin 2 (LECT2) causes ALECT2, a systemic amyloidosis that affects the kidney and liver. Previous studies established that LECT2 fibrillogenesis is accelerated by the loss of its bound zinc ion and stirring/shaking. These forms of agitation create heterogeneous shear conditions, including air-liquid interfaces that denature proteins, that are not present in
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TRIM13 reduces cholesterol efflux and increases oxidized LDL uptake leading to foam cell formation and atherosclerosis J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-25 Suresh Govatati, Raj Kumar, Monoranjan Boro, James G. Traylor Jr., A. Wayne Orr, Aldons J. Lusis, Gadiparthi N. Rao
Impaired cholesterol efflux and/or uptake can influence arterial lipid accumulation leading to atherosclerosis. Here, we report that tripartite motif-containing protein 13 (TRIM13), a RING-type E3 ubiquitin ligase, plays a role in arterial lipid accumulation leading to atherosclerosis. Using molecular approaches and KO mouse model, we found that TRIM13 expression was induced both in the aorta and peritoneal
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Structural insight into the ZFAND1–p97 interaction involved in stress granule clearance J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-25 Chih-Hsuan Lai, Kuang-Ting Ko, Pei-Ju Fan, Tsun-Ai Yu, Chi-Fon Chang, Piotr Draczkowski, Shang-Te Danny Hsu
Arsenite-induced stress granule (SG) formation can be cleared by the ubiquitin-proteasome system aided by the ATP-dependent unfoldase p97. ZFAND1 participates in this pathway by recruiting p97 to trigger SG clearance. ZFAND1 contains two An1-type zinc finger domains (ZF1 and ZF2), followed by a ubiquitin-like domain (UBL); but their structures are not experimentally determined. To shed light on the
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Mouse mucosal-associated invariant T cell receptor recognition of MR1 presenting the vitamin B metabolite, 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-25 Lisa Ciacchi, Jeffrey Y.W. Mak, Jeremy P. Le, David P. Fairlie, James McCluskey, Alexandra J. Corbett, Jamie Rossjohn, Wael Awad
Mucosal-associated invariant T (MAIT) cells can elicit immune responses against riboflavin-based antigens presented by the evolutionary conserved MHC class I related-1 protein, MR1. While we have an understanding of the structural basis of human MAIT cell receptor (TCR) recognition of human MR1 presenting a variety of ligands, how the semi-invariant mouse MAIT TCR binds mouse MR1-ligand remains unknown
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Epstein-Barr virus suppresses N6-methyladenosine modification of TLR9 to promote immune evasion J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-25 Xiaoyue Zhang, Zhengshuo Li, Qiu Peng, Can Liu, Yangge Wu, Yuqing Wen, Run Zheng, Chenxiao Xu, Junrui Tian, Xiang Zheng, Qun Yan, Jia Wang, Jian Ma
Epstein-Barr virus (EBV) is a human tumor virus associated with a variety of malignancies, including nasopharyngeal carcinoma, gastric cancers, and B-cell lymphomas. N-methyladenosine (mA) modifications modulate a wide range of cellular processes and participate in the regulation of virus-host cell interactions. Here, we discovered that EBV infection downregulates toll-like receptor 9 (TLR9) mA modification
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Abstract 2475 Quantifying the Repression and Induction of LacI/GalR Chimeric Proteins J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-25 Chris Elniff, Carter Gray, Sophia Bock, Phalgun Pandi, Tejpreet Kaur
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Abstract 2456 For a Few Dollars More: Treatment of Metastatic Head and Neck Cancers with Dimerized CXCL12 J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-25 Stacey Strandberg, Daniela Basurto-Sil, Annabelle Leh, Atenea Diaz, Anna O'Brien, Elizabeth Regan, Alexandra Schneider, Ella Wurtzbacher
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Abstract 2439 The Good, the Bad, and the Ugly of Chemokines: Inhibiting CXCR4 to Stop Metastasis of Head and Neck Cancers J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-25 Stacey Strandberg, Charlotte Desjarlais, Ilse Hilander, Ella Jankowski, Katherine Mark, Josie Marsho, Helen Pollock, Sawyer Strandberg
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Abstract 2437 Neuroplasticity in Alzheimer's Treatment: The Impact of Psychedelic-Induced TrkB Activation J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-25 Katherine Alex, Ethan Cabalona, Matviy(Matvei) Amchislavskiy, Phillip Neff, Caleb Silver, Donald Williamson, Cecileah Wang
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Abstract 2436 Molecular Interactions of SERT and Escitalopram in Serotonin Modulation J. Biol. Chem. (IF 5.5) Pub Date : 2024-03-25 Katherine Alex, Yiming Zhao, Xuhong Ding, Latiyfa Fayzullaeva, Amy Ge, Maeve O'Donnell, Chengyun (Edward) Shen