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Polymer-based antibody mimetics (iBodies) target human PD-L1 and function as a potent immune checkpoint blocker J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-27 Mohammad Reza Zamani, Martin Hadzima, Kristyna Blazkova, Vladimír Šubr, Tereza Ormsby, Javier Celis-Gutierrez, Bernard Malissen, Libor Kostka, Tomáš Etrych, Pavel Šácha, Jan Konvalinka
Immune checkpoint blockade (ICB) using monoclonal antibodies against programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) is the treatment of choice for cancer immunotherapy. However, low tissue permeability, immunogenicity, immune-related adverse effects, and high cost could be possibly improved using alternative approaches. On the other hand, synthetic low-molecular-weight
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Discovery and development of macrocyclic peptide modulators of the cannabinoid 2 receptor J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-26 Nataša Tomašević, Fabiola Susanna Emser, Edin Muratspahić, Jasmin Gattringer, Simon Hasinger, Roland Hellinger, Peter Keov, Manuel Felkl, Jürg Gertsch, Christian F.W. Becker, Christian W. Gruber
The cannabinoid-type 2 receptor (CBR), a G protein–coupled receptor, is an important regulator of immune cell function and a promising target to treat chronic inflammation and fibrosis. While CBR is typically targeted by small molecules, including endo-, phyto-, and synthetic cannabinoids, peptides–owing to their size–may offer a different interaction space to facilitate differential interactions with
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Molecular basis for dual functions in pilus assembly modulated by the lid of a pilus-specific sortase J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-26 Chungyu Chang, HyLam Ton-That, Jerzy Osipiuk, Andrzej Joachimiak, Asis Das, Hung Ton-That
The biphasic assembly of Gram-positive pili begins with the covalent polymerization of distinct pilins catalyzed by a pilus-specific sortase, followed by the cell wall anchoring of the resulting polymers mediated by the housekeeping sortase. In , the pilus-specific sortase SrtC2 not only polymerizes FimA pilins to assemble type 2 fimbriae with CafA at the tip, but it can also act as the anchoring sortase
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Adipose tissue macrophage–derived microRNA-210-3p disrupts systemic insulin sensitivity by silencing GLUT4 in obesity J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-26 Debarun Patra, Palla Ramprasad, Shivam Sharma, Upalabdha Dey, Vinod Kumar, Satpal Singh, Suman Dasgupta, Aditya Kumar, Kulbhushan Tikoo, Durba Pal
Management of chronic obesity-associated metabolic disorders is a key challenge for biomedical researchers. During chronic obesity, visceral adipose tissue (VAT) undergoes substantial transformation characterized by a unique lipid-rich hypoxic AT microenvironment which plays a crucial role in VAT dysfunction, leading to insulin resistance (IR) and type 2 diabetes. Here, we demonstrate that obese AT
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Brefeldin A and M-COPA block the export of RTKs from the endoplasmic reticulum via simultaneous inactivation of ARF1, ARF4, and ARF5 J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-26 Miyuki Natsume, Mariko Niwa, Sho Ichikawa, Takuma Okamoto, Hisazumi Tsutsui, Daiki Usukura, Takatsugu Murata, Ryo Abe, Motoyuki Shimonaka, Toshirou Nishida, Isamu Shiina, Yuuki Obata
Normal receptor tyrosine kinases (RTKs) need to reach the plasma membrane (PM) for ligand-induced activation, whereas its cancer-causing mutants can be activated before reaching the PM in organelles, such as the Golgi/-Golgi network (TGN). Inhibitors of protein export from the endoplasmic reticulum (ER), such as brefeldin A (BFA) and 2-methylcoprophilinamide (M-COPA), can suppress the activation of
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Milligram-scale assembly and NMR fingerprint of tau fibrils adopting the Alzheimer’s disease fold J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-26 Pu Duan, Nadia El Mammeri, Mei Hong
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A minimum functional form of the Escherichia coli BAM complex constituted by BamADE assembles outer membrane proteins in vitro J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-25 Zhe Wang, Yindi Chu, Qingrong Li, Xiaochen Han, Leyi Zhao, Hanqing Zhang, Kun Cai, Xuyan Zhang, Xingyuan Wang, Youcai Qin, Enguo Fan
The biogenesis of outer membrane proteins is mediated by the -barrel ssembly achinery (BAM), which is a heteropentomeric complex composed of five proteins named BamA-E in . Despite great progress in the BAM structural analysis, the molecular details of BAM-mediated processes as well as the exact function of each BAM component during OMP assembly are still not fully understood. To enable a distinguishment
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The types and numbers of kinesins and dyneins transporting endocytic cargoes modulate their motility and response to tau J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-25 Daniel Beaudet, Christopher L. Berger, Adam G. Hendricks
Organelles and vesicular cargoes are transported by teams of kinesin and dynein motors along microtubules. We isolated endocytic organelles from cells at different stages of maturation and reconstituted their motility along microtubules . We asked how the sets of motors transporting a cargo determine its motility and response to the microtubule-associated protein tau. Here, we find that phagosomes
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Spatial transcriptomics unravels palmitoylation and zonation-dependent gene regulation by AEG-1 in mouse liver J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-25 Alissa Saverino, Xufeng Qu, Rachel G. Mendoza, Suchismita Raha, Debashri Manna, Ali Gawi Ermi, Mark A. Subler, Jolene J. Windle, Jinze Liu, Devanand Sarkar
Obesity-induced metabolic dysfunction-associated steatohepatitis (MASH) leads to hepatocellular carcinoma (HCC). Astrocyte-elevated gene-1/Metadherin (AEG-1/MTDH) plays a key role in promoting MASH and HCC. AEG-1 is palmitoylated at residue cysteine 75 (Cys75) and a knock-in mouse representing mutated Cys75 to serine (AEG-1-C75S) showed activation of MASH- and HCC-promoting gene signature when compared
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Loss of the ceramide synthase HYL-2 from Caenorhabditis elegans impairs stress responses and alters sphingolipid composition J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-25 Huaiyi Zhu, Yunfei You, Boming Yu, Zhitao Deng, Min Liu, Zhenying Hu, Jingjing Duan
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Senp7 deficiency impairs lipid droplets maturation in white adipose tissues via Plin4 deSUMOylation J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-25 Jingwen Pei, Dayuan Zou, Lu Li, Lulu Kang, Minli Sun, Xu Li, Qianyue Chen, Danning Chen, Bin Qu, Xiang Gao, Zhaoyu Lin
Lipid metabolism is important for the maintenance of physiological homeostasis. Several members of the small ubiquitin-like modifier (SUMO)-specific protease (SENP) family have been reported as the regulators of lipid homeostasis. However, the function of Senp7 in lipid metabolism remains unclear. In this study, we generated both conventional and adipocyte-specific KO mice to characterize the role
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The discovery of a catalytic RNA within RNase P and its legacy J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-25 Leif A. Kirsebom, Fenyong Liu, William H. McClain
Sidney Altman's discovery of the processing of one RNA by another RNA that acts like an enzyme was revolutionary in biology and the basis for his sharing the 1989 Nobel Prize in Chemistry with Tom Cech. These breakthrough findings support the key role of RNA in molecular evolution, where replicating RNAs (and similar chemical derivatives) either with or without peptides functioned in protocells during
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Probing RNA structure and dynamics using nanopore and next generation sequencing J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-25 Emma Bose, Shengwei Xiong, Alisha N. Jones
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Inhibition of neuraminidase-1 sialidase activity by interfering peptides impairs insulin receptor activity in vitro and glucose homeostasis in vivo J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-23 Kevin Toussaint, Aline Appert-Collin, Laetitia Vanalderwiert, Camille Bour, Christine Terryn, Caroline Spenlé, Michaël Van Der Heyden, Mathilde Roumieux, Pascal Maurice, Béatrice Romier-Crouzet, Hervé Sartelet, Laurent Duca, Sébastien Blaise, Amar Bennasroune
Neuraminidases (NEUs) also called sialidases are glycosidases which catalyze the removal of terminal sialic acid residues from glycoproteins, glycolipids, and oligosaccharides. Mammalian NEU-1 participates in regulation of cell surface receptors such as insulin receptor (IR), epithelial growth factor receptor, low density lipoprotein receptor, and toll like receptor 4. At the plasma membrane, NEU-1
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Hotspot site microenvironment in the deubiquitinase OTUB1 drives its stability and aggregation J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-23 Sushanta Majumder, Mitul Srivastava, Parvez Alam, Sandhini Saha, Raniki Kumari, Ajay Kumar Chand, Shailendra Asthana, Sobhan Sen, Tushar Kanti Maiti
Lewy bodies (LB) are aberrant protein accumulations observed in the brain cells of individuals affected by Parkinson's disease (PD). A comprehensive analysis of LB proteome identified over a hundred proteins, many co-enriched with α-synuclein, a major constituent of LB. Within this context, OTUB1, a deubiquitinase detected in LB, exhibits amyloidogenic properties, yet the mechanisms underlying its
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SORL1 is a receptor for tau that promotes tau seeding J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-23 Joanna M. Cooper, Aurelien Lathuiliere, Enming J. Su, Yuyu Song, Daniel Torrente, Youhwa Jo, Nicholas Weinrich, Jennifer Diaz Sales, Mary Migliorini, Thomas H. Sisson, Daniel A. Lawrence, Bradley T. Hyman, Dudley K. Strickland
Sortilin-related receptor 1 (SORL1) is an intracellular sorting receptor genetically implicated in Alzheimer’s disease (AD) that impacts amyloid precursor protein trafficking. The objective of these studies was to test the hypothesis that SORL1 binds tau, modulates its cellular trafficking and impacts the aggregation of cytoplasmic tau induced by pathological forms of tau. Using surface plasmon resonance
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Vitamin A enhanced periosteal osteoclastogenesis is associated with increased number of tissue-derived macrophages/osteoclast progenitors J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-23 Petra Henning, Anna Westerlund, Karin Horkeby, Vikte Lionikaite, Karin H. Nilsson, Sofia Movérare-Skrtic, H. Herschel Conaway, Ulf H. Lerner
A deleterious effect of elevated levels of vitamin A on bone health has been reported in numerous clinical studies. Mechanistic studies in rodents have shown that numbers of periosteal osteoclasts are increased, while endocortical osteoclasts are simultaneously decreased by vitamin A treatment. These observations indicate that osteoclastogenesis on the endocortical and periosteal surfaces of bone is
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PTIP UFMylation promotes replication fork degradation in BRCA1-deficient cells J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-22 Qunsong Tan, Xingzhi Xu
“BRCAness” defines cancers that are homologous recombination–deficient due to breast cancer 1 (BRCA1) or BRCA2 mutations. These mutations confer synthetic lethality with poly-(ADP)-ribose polymerase 1/2 inhibitors. The chromatin regulator Pax2 transactivation domain interacting protein (PTIP) promotes stalled replication fork degradation in “BRCAness” cells, but the underlying mechanism by which PTIP
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Reactivating Hippo by drug compounds to suppress gastric cancer and enhance chemotherapy sensitivity J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-22 Zhifa Cao, Yu Hou, Zhangting Zhao, Hui Zhang, Luyang Tian, Yiming Zhang, Chao Dong, Fenghua Guo, Lijie Tan, Yi Han, Wenjia Wang, Shi Jiao, Yang Tang, Liwei An, Zhaocai Zhou
The Hippo signaling pathway plays an essential role in organ size control and tumorigenesis. Loss of Hippo signal and hyper-activation of the downstream oncogenic YAP signaling are commonly observed in various types of cancers. We previously identified STRN3-containing PP2A phosphatase as a negative regulator of MST1/2 kinases (, Hippo) in gastric cancer (GC), opening the possibility of selectively
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Blockade of a novel MAP4K4-LATS2-SASH1-YAP1 cascade inhibits tumorigenesis and metastasis in luminal breast cancer J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-22 Pingping Yang, Yadong Li, Jing Hou, Daoqiu Wu, Xing Zeng, Zhen Zeng, Jing Zhang, Yu Xiong, Lian Chen, Dan Yang, Xin Wan, Zhixiong Wu, Lei Jia, Qianfan Liu, Qingxiang Lu, Xue Zou, Wen Fang, Xiaohua Zeng, Ding’an Zhou
Novel components in the noncanonical Hippo pathway that mediate the growth, metastasis, and drug resistance of breast cancer (BC) cells need to be identified. Here, we showed that expression of SAM and SH3 domain-containing protein 1 (SASH1) is negatively correlated with expression of mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) in a subpopulation of patients with luminal-subtype
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The role of histone H3 leucine 126 in fine-tuning the copper reductase activity of nucleosomes J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-22 Nataliya P. Tod, Maria Vogelauer, Chen Cheng, Ansar Karimian, Stefan Schmollinger, Dimitrios Camacho, Siavash K. Kurdistani
The copper reductase activity of histone H3 suggests undiscovered characteristics within the protein. Here, we investigated the function of leucine 126 (H3L126), which occupies an axial position relative to the copper binding. Typically found as methionine or leucine in copper-binding proteins, the axial ligand influences the reduction potential of the bound ion, modulating its tendency to accept or
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Liquid–liquid phase separation of the prion protein is regulated by the octarepeat domain independently of histidines and copper J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-22 Janine Kamps, Verian Bader, Konstanze F. Winklhofer, Jörg Tatzelt
Liquid-liquid phase separation (LLPS) of the mammalian prion protein is mainly driven by its intrinsically disordered N-terminal domain (N-PrP). However, the specific intermolecular interactions that promote LLPS remain largely unknown. Here, we used extensive mutagenesis and comparative analyses of evolutionarily distant PrP species to gain insight into the relationship between protein sequence and
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African swine fever virus infection regulates pyroptosis by cleaving gasdermin A via active caspase-3 and caspase-4 J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-22 Shuai Li, Jie Song, jia Liu, Shijun Zhou, Gaihong Zhao, Tingting Li, Li Huang, Jiangnan Li, Changjiang Weng
African swine fever, caused by the African swine fever virus (ASFV), is a viral hemorrhagic disease that affects domestic pigs and wild boars. ASFV infection causes extensive tissue damage, and the associated mechanism is poorly understood. Pyroptosis is characterized by the activation of inflammatory caspases and pore formation in the cellular plasma membrane, resulting in the release of inflammatory
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Zinc utilization by microglia in Alzheimer’s disease J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-20 Daniel C. Shippy, Sophia F. Oliai, Tyler K. Ulland
Alzheimer’s disease (AD) is the most common form of dementia defined by two key pathological characteristics in the brain, amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau. Microglia, the primary innate immune cells of the central nervous system (CNS), provide neuroprotection through Aβ and tau clearance but may also be neurotoxic by promoting neuroinflammation
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Critical amino acid residues regulating TRPA1 Zn2+ response: A comparative study across species J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-18 Masaki Matsubara, Yukiko Muraki, Hiroka Suzuki, Noriyuki Hatano, Katsuhiko Muraki
Cellular zinc ions (Zn) are crucial for signal transduction in various cell types. The transient receptor potential (TRP) ankyrin 1 (TRPA1) channel, known for its sensitivity to intracellular Zn ([Zn]), has been a subject of limited understanding regarding its molecular mechanism. Here, we used metal ion-affinity prediction, three-dimensional structural modeling, and mutagenesis, utilizing data from
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Defining the mechanism of galectin-3–mediated TGF-β1 activation and its role in lung fibrosis J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-18 Jessica F. Calver, Nimesh R. Parmar, Gemma Harris, Ryan M. Lithgo, Panayiota Stylianou, Fredrik R. Zetterberg, Bibek Gooptu, Alison C. Mackinnon, Stephen B. Carr, Lee A. Borthwick, David J. Scott, Iain D. Stewart, Robert J. Slack, R. Gisli Jenkins, Alison E. John
Integrin-mediated activation of the profibrotic mediator transforming growth factor-β1 (TGF-β1), plays a critical role in idiopathic pulmonary fibrosis (IPF) pathogenesis. Galectin-3 is believed to contribute to the pathological wound healing seen in IPF, although its mechanism of action is not precisely defined. We hypothesized that galectin-3 potentiates TGF-β1 activation and/or signaling in the
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ABCG2 and SLC1A5 functionally interact to rewire metabolism and confer a survival advantage to cancer cells under oxidative stress J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-18 Jia Shi, Kirk Pabon, Rui Ding, Kathleen W. Scotto
ABCG2, a member of the ABC transporter superfamily, is overexpressed in many human tumors and has long been studied for its ability to export a variety of chemotherapeutic agents, thereby conferring a multidrug resistance (MDR) phenotype. However, several studies have shown that ABCG2 can also confer an MDR- survival advantage to tumor cells exposed to stress. While investigating the mechanism by which
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LncRNA-SERB promotes vasculogenic mimicry (VM) formation and tumor metastasis in renal cell carcinoma J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-18 Shuai Tang, Fangmin Chen, Jianghui Zhang, Fan Chang, Zheng Lv, Kai Li, Song Li, Yixi Hu, Shuyuan Yeh
A growing body of evidence shows that vasculogenic mimicry (VM) is closely related to the invasion and metastasis of many tumor cells. Although the estrogen receptor (ER) can promote initiation and progression of renal cell carcinoma (RCC), how the downstream biomolecules are involved, and the detailed mechanisms of how ER expression is elevated in RCC remain to be further elucidated. Here, we discovered
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Unity among the diverse RNA-guided CRISPR-Cas interference mechanisms J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-18 Chhandosee Ganguly, Saadi Rostami, Kole Long, Swarmistha Devi Aribam, Rakhi Rajan
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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-GlcNAc is an essential posttranslational modification, which is 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, and metabolism
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Rapid HPLC method reveals dynamic shifts in coenzyme Q redox state J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-17 Victor Vitvitsky, Roshan Kumar, Jutta Diessl, David A. Hanna, Ruma Banerjee
Ubiquinol or coenzyme Q (CoQ) is a lipid-soluble electron carrier in the respiratory chain and an electron acceptor for various enzymes in metabolic pathways that intersect at this cofactor hub in the mitochondrial inner membrane. The reduced form of CoQ is an antioxidant, which protects against lipid peroxidation. In this study, we have optimized a UV-detected HPLC method for CoQ analysis from biological
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Exenatide reduces atrial fibrillation susceptibility by inhibiting hKv1.5 and hNav1.5 channels J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-16 Qian Zhou, Guoliang Hao, Wensen Xie, Bin Chen, Wuguang Lu, Gongxin Wang, Rongling Zhong, Jiao Chen, Juan Ye, Jianping Shen, Peng Cao
Exenatide, a promising cardioprotective agent, protects against cardiac structural remodeling and diastolic dysfunction. Combined blockade of sodium and potassium channels is valuable for managing atrial fibrillation (AF). Here, we explored whether exenatide displayed anti-AF effects by inhibiting human Kv1.5 and Nav1.5 channels. We used the whole-cell patch-clamp technique to investigate the effects
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The Michael addition of thiols to 13-oxo-octadecadienoate (13-oxo-ODE) with implications for LC-MS analysis of glutathione conjugation J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-16 William E. Boeglin, Donald F. Stec, Saori Noguchi, M. Wade Calcutt, Alan R. Brash
Unsaturated fatty acid ketones with αβ,γδ conjugation are susceptible to Michael addition of thiols, with unresolved issues on the site of adduction and precise structures of the conjugates. Herein we reacted 13-keto-octadecadienoic acid (13-oxo-ODE or 13-KODE) with glutathione (GSH), N-acetyl-cysteine, and β-mercaptoethanol and identified the adducts. HPLC-UV analyses indicated none of the products
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Properties of the iron-sulfur cluster electron transfer relay in an [FeFe]-hydrogenase that is tuned for H2 oxidation catalysis J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-16 Effie C. Kisgeropoulos, Jacob H. Artz, Matthew Blahut, John W. Peters, Paul W. King, David W. Mulder
[FeFe]-hydrogenases catalyze the reversible oxidation of H from electrons and protons at an organometallic active site cofactor named the H-cluster. In addition to the H-cluster, most [FeFe]-hydrogenases possess accessory FeS cluster (F-cluster) relays that function in mediating electron transfer with catalysis. There is significant variation in the structural properties of F-cluster relays among the
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Restoring retinal polyunsaturated fatty acid balance and retina function by targeting ceramide in AdipoR1-deficient mice J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-16 Dominik Lewandowski, Fangyuan Gao, Sanae Imanishi, Aleksander Tworak, Marco Bassetto, Zhiqian Dong, Antonio F.M. Pinto, Marcin Tabaka, Philip D. Kiser, Yoshikazu Imanishi, Dorota Skowronska-Krawczyk, Krzysztof Palczewski
Mutations in the adiponectin receptor 1 gene () lead to retinitis pigmentosa and are associated with age-related macular degeneration. This study explores the effects of AdipoR1 gene deficiency in mice, revealing a striking decline in ω3 polyunsaturated fatty acids (PUFA), an increase in ω6 fatty acids, and elevated ceramides in the retina. The AdipoR1 deficiency impairs peroxisome proliferator-activated
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Inability to rescue stalled ribosomes results in overactivation of the integrated stress response J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-16 Ankanahalli N. Nanjaraj Urs, Victor Lasehinde, Lucas Kim, Elesa McDonald, Liewei L. Yan, Hani S. Zaher
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Cryo-EM structure of human HCN3 channel and its regulation by cAMP J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-16 Bo Yu, Qiuyuan Lu, Jian Li, Xinyu Cheng, Han Hu, Yuanshuo Li, Tong Che, Yaoguang Hua, Haihai Jiang, Yuting Zhang, Cuiling Xian, Tingting Yang, Ying Fu, Yixiang Chen, Weiwei Nan, Peter J. McCormick, Bing Xiong, Jingjing Duan, Bo Zeng, Yanyan Li, Yang Fu, Jin Zhang
HCN channels are important for regulating heart rhythm and nerve activity and have been studied as potential drug targets for treating depression, arrhythmia, nerve pain, and epilepsy. Despite possessing unique pharmacological properties, HCN channels share common characteristics in that they are activated by hyperpolarization and modulated by cAMP and other membrane lipids. However, the mechanisms
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Proximity labeling of host factor ANXA3 in HCV infection reveals a novel LARP1 function in viral entry J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-16 Hanna Bley, Christoph Krisp, Anja Schöbel, Julia Hehner, Laura Schneider, Miriam Becker, Cora Stegmann, Elisa Heidenfels, Van Nguyen-Dinh, Hartmut Schlüter, Gisa Gerold, Eva Herker
Hepatitis C virus (HCV) infection is tightly connected to the lipid metabolism with lipid droplets (LDs) serving as assembly sites for progeny virions. A previous LD proteome analysis identified annexin A3 (ANXA3) as an important HCV host factor that is enriched at LDs in infected cells and required for HCV morphogenesis. To further characterize ANXA3 function in HCV, we performed proximity labeling
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The Plasmodium vivax MSP1P-19 is involved in binding of reticulocytes through interactions with the membrane proteins band3 and CD71 J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-16 Shenghuan Zuo, Jiachen Lu, Yifan Sun, Jing Song, Su Han, Xin Feng, Eun-Taek Han, Yang Cheng
The parasite preferentially invades human reticulocytes. Its merozoite surface protein 1 paralog (PvMSP1P), particularly the 19-kDa C-terminal region (PvMSP1P-19), has been shown to bind to reticulocytes, and this binding can be inhibited by antisera obtained by PvMSP1P-19 immunization. The molecular mechanism of interactions between PvMSP1P-19 and reticulocytes during invasion, however, remains unclear
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The structure of the rat vitamin B12 transporter TC and its complex with glutathionylcobalamin J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-16 Marcel Bokhove, Takashi Kawamura, Hideo Okumura, Sawako Goto, Yoshiaki Kawano, Stefan Werner, Franziska Jarczowski, Victor Klimyuk, Akihiko Saito, Takashi Kumasaka
Vitamin B (cobalamin or Cbl) functions as a cofactor in two important enzymatic processes in human cells, and life is not sustainable without it. B is obtained from food and travels from the stomach, through the intestine, and into the bloodstream by three B-transporting proteins: salivary haptocorrin (HC), gastric intrinsic factor, and transcobalamin (TC), which all bind B with high affinity and require
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Cyclic AMP binding to a universal stress protein in Mycobacterium tuberculosis is essential for viability J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-16 Arka Banerjee, Moubani Chakraborty, Suruchi Sharma, Ruchi Chaturvedi, Avipsa Bose, Priyanka Biswas, Amit Singh, Sandhya S. Visweswariah
Mycobacterial genomes encode multiple adenylyl cyclases and cAMP effector proteins, underscoring the diverse ways these bacteria utilize cAMP. We identified universal stress proteins, Rv1636 and MSMEG_3811 in and respectively, as abundantly expressed, novel cAMP-binding proteins. Rv1636 is secreted the SecA2 secretion system in but is not directly responsible for the efflux of cAMP from the cell. In
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A proteomics-based survey reveals thrombospondin-4 as a ligand regulated by the mannose receptor in the injured lung J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-13 Kirstine S. Nørregaard, Henrik J. Jürgensen, Signe S. Heltberg, Henrik Gårdsvoll, Thomas H. Bugge, Erwin M. Schoof, Lars H. Engelholm, Niels Behrendt
Receptor-mediated cellular uptake of specific ligands constitutes an important step in the dynamic regulation of individual protein levels in extracellular fluids. With a focus on the inflammatory lung, we here performed a proteomics-based search for novel ligands regulated by the mannose receptor (MR), a macrophage-expressed endocytic receptor. WT and MR-deficient mice were exposed to lipopolysaccharide
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Utility of protein–protein binding surfaces composed of anti-parallel alpha-helices and beta-sheets selected by phage display J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-11 Ningyu Zhu, Philip M. Smallwood, Amir Rattner, Tao-Hsin Chang, John Williams, Yanshu Wang, Jeremy Nathans
Over the past 3 decades, a diverse collection of small protein domains have been used as scaffolds to generate general purpose protein-binding reagents using a variety of protein display and enrichment technologies. To expand the repertoire of scaffolds and protein surfaces that might serve this purpose, we have explored the utility of (i) a pair of anti-parallel alpha-helices in a small highly disulfide-bonded
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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 its extreme hydrophobicity and high molecular weight. 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 neuronal nicotinic receptor alters intra- and inter-subunit 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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Correction: Analysis of Poly(ethylene terephthalate) degradation kinetics of evolved IsPETase variants using a surface crowding mode J. Biol. Chem. (IF 5.5) Pub Date : 2024-04-04 En Ze Linda Zhong-Johnson, Ziyue Dong, Christopher T. Canova, Francesco Destro, Marina Cañellas, Mikaila C. Hoffman, Jeanne Maréchal, Timothy M. Johnson, Maya Zheng, Gabriela S. Schlau-Cohen, Maria Fátima Lucas, Richard D. Braatz, Kayla G. Sprenger, Christopher A. Voigt, Anthony J. Sinskey