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Calcium binds and rigidifies the dysferlin C2A domain in a tightly coupled manner Biochem. J. (IF 4.097) Pub Date : 2021-01-15 Wang, Yuning; Tadayon, Roya; Santamaria, Liliana; Mercier, Pascal; Forristal, Chantal J.; Shaw, Gary S.
The membrane protein dysferlin (DYSF) is important for calcium-activated plasma membrane repair, especially in muscle fibre cells. Nearly 600 mutations in the DYSF gene have been identified that are causative for rare genetic forms of muscular dystrophy. The dysferlin protein consists of seven C2 domains (C2A–C2G, 13%–33% identity) used to recruit calcium ions and traffic accessory proteins and vesicles
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Stability of Smyd1 in endothelial cells is controlled by PML-dependent SUMOylation upon cytokine stimulation Biochem. J. (IF 4.097) Pub Date : 2021-01-15 Becker, Samuel; Steinemann, Gustav; Karle, Weronika; Roos, Kerrin; Liem, Celine Huajia; Muralikumar, Shalini; Volkamer, Andrea; Munz, Barbara; Zakrzewicz, Andreas; Berkholz, Janine
Smyd1 is an epigenetic modulator of gene expression that has been well-characterized in muscle cells. It was recently reported that Smyd1 levels are modulated by inflammatory processes. Since inflammation affects the vascular endothelium, this study aimed to characterize Smyd1 expression in endothelial cells. We detected Smyd1 in human endothelial cells (HUVEC and EA.hy926 cells), where the protein
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Inhibition of d-glycero-β-d-manno-heptose 1-phosphate adenylyltransferase from Burkholderia pseudomallei by epigallocatechin gallate and myricetin Biochem. J. (IF 4.097) Pub Date : 2021-01-15 Kim, Suwon; Jo, Seri; Kim, Mi-Sun; Kam, Heejin; Shin, Dong Hae
Flavonoids play beneficial roles in various human diseases. In this study, a flavonoid library was employed to probe inhibitors of d-glycero-β-d-manno-heptose-1-phosphate adenylyltransferase from Burkholderia pseudomallei (BpHldC) and two flavonoids, epigallocatechin gallate (EGCG) and myricetin, have been discovered. BpHldC is one of the essential enzymes in the ADP-l-glycero-β-d-manno-heptose biosynthesis
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The RNA-binding protein HuR regulates intestinal epithelial restitution by modulating Caveolin-1 gene expression Biochem. J. (IF 4.097) Pub Date : 2021-01-15 Cao, Shan; Xiao, Lan; Wang, Junyao; Chen, Guodong; Liu, Yulan
The integrity of the intestinal mucosal barrier protects hosts against pathological conditions. Early mucosal restitution after wounding refers to epithelial cell migration into a defect. The RNA-binding protein HuR plays an important role in the posttranscriptional regulation of gene expression and is involved in many aspects of cellular physiology. In the present study, we investigated the role of
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Herpes simplex virus 1 infection induces ubiquitination of UBE1a Biochem. J. (IF 4.097) Pub Date : 2021-01-15 Ikeda, Marina; Watanabe, Tadashi; Ito, Akihiro; Fujimuro, Masahiro
Herpes simplex virus 1 (HSV-1) is a human DNA virus that causes cold sores, keratitis, meningitis, and encephalitis. Ubiquitination is a post-translational protein modification essential for regulation of cellular events, such as proteasomal degradation, signal transduction, and protein trafficking. The process is also involved in events for establishing viral infection and replication. The first step
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Extracellular signal-regulated kinase (ERK) pathway control of CD8+ T cell differentiation Biochem. J. (IF 4.097) Pub Date : 2021-01-15 Damasio, Marcos P.; Marchingo, Julia M.; Spinelli, Laura; Hukelmann, Jens L.; Cantrell, Doreen A.; Howden, Andrew J.M.
The integration of multiple signalling pathways that co-ordinate T cell metabolism and transcriptional reprogramming is required to drive T cell differentiation and proliferation. One key T cell signalling module is mediated by extracellular signal-regulated kinases (ERKs) which are activated in response to antigen receptor engagement. The activity of ERKs is often used to report antigen receptor occupancy
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Hydrogen deuterium exchange mass spectrometry identifies the dominant paratope in CD20 antigen binding to the NCD1.2 monoclonal antibody Biochem. J. (IF 4.097) Pub Date : 2021-01-15 Uhrik, Lukas; Hernychova, Lenka; Muller, Petr; Kalathiya, Umesh; Lisowska, Malgorzata M.; Kocikowski, Mikolaj; Parys, Maciej; Faktor, Jakub; Nekulova, Marta; Nortcliffe, Chris; Zatloukalova, Pavlina; Ruetgen, Barbara; Fahraeus, Robin; Ball, Kathryn L.; Argyle, David J.; Vojtesek, Borivoj; Hupp, Ted R.
A comparative canine–human therapeutics model is being developed in B-cell lymphoma through the generation of a hybridoma cell that produces a murine monoclonal antibody specific for canine CD20. The hybridoma cell produces two light chains, light chain-3, and light chain-7. However, the contribution of either light chain to the authentic full-length hybridoma derived IgG is undefined. Mass spectrometry
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Weakening of interaction networks with aging in tip-link protein induces hearing loss Biochem. J. (IF 4.097) Pub Date : 2021-01-15 Garg, Surbhi; Sagar, Amin; Singaraju, Gayathri S.; Dani, Rahul; Bari, Naimat K.; Naganathan, Athi N.; Rakshit, Sabyasachi
Age-related hearing loss (ARHL) is a common condition in humans marking the gradual decrease in hearing with age. Perturbations in the tip-link protein cadherin-23 that absorbs the mechanical tension from sound and maintains the integrity of hearing is associated with ARHL. Here, in search of molecular origins for ARHL, we dissect the conformational behavior of cadherin-23 along with the mutant S47P
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Hyperthermia induced disruption of mechanical balance leads to G1 arrest and senescence in cells Biochem. J. (IF 4.097) Pub Date : 2021-01-15 Mundhara, Nikita; Majumder, Abhijit; Panda, Dulal
Human body temperature limits below 40°C during heat stroke or fever. The implications of prolonged exposure to the physiologically relevant temperature (40°C) on cellular mechanobiology is poorly understood. Here, we have examined the effects of heat stress (40°C for 72 h incubation) in human lung adenocarcinoma (A549), mouse melanoma (B16F10), and non-cancerous mouse origin adipose tissue cells (L929)
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Structural insights into DNA double-strand break signaling Biochem. J. (IF 4.097) Pub Date : 2021-01-15 Panigrahi, Rashmi; Glover, J. N. Mark
Genomic integrity is most threatened by double-strand breaks, which, if left unrepaired, lead to carcinogenesis or cell death. The cell generates a network of protein–protein signaling interactions that emanate from the DNA damage which are now recognized as a rich basis for anti-cancer therapy development. Deciphering the structures of signaling proteins has been an uphill task owing to their large
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The role of chemical biology in the fight against SARS-CoV-2 Biochem. J. (IF 4.097) Pub Date : 2021-01-15 Burslem, George M.
Since late 2019, biomedical labs all over the world have been struggling to cope with the ‘new normal' and to find ways in which they can contribute to the fight against COVID-19. In this unique situation where a biomedical issue dominates people's lives and the news cycle, chemical biology has a great deal to contribute. This review will describe the importance of science at the chemistry/biology
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Calcitriol increases frataxin levels and restores mitochondrial function in cell models of Friedreich Ataxia Biochem. J. (IF 4.097) Pub Date : 2021-01-15 Britti, Elena; Delaspre, Fabien; Sanz-Alcázar, A.; Medina-Carbonero, Marta; Llovera, Marta; Purroy, Rosa; Mincheva-Tasheva, Stefka; Tamarit, Jordi; Ros, Joaquim
Friedreich ataxia (FA) is a neurodegenerative disease caused by the deficiency of frataxin, a mitochondrial protein. In primary cultures of dorsal root ganglia neurons, we showed that frataxin depletion resulted in decreased levels of the mitochondrial calcium exchanger NCLX, neurite degeneration and apoptotic cell death. Here, we describe that frataxin-deficient dorsal root ganglia neurons display
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Patient-derived glioblastoma stem cells transfer mitochondria through tunneling nanotubes in tumor organoids Biochem. J. (IF 4.097) Pub Date : 2021-01-15 Pinto, Giulia; Saenz-de-Santa-Maria, Inés; Chastagner, Patricia; Perthame, Emeline; Delmas, Caroline; Toulas, Christine; Moyal-Jonathan-Cohen, Elizabeth; Brou, Christel; Zurzolo, Chiara
Glioblastoma (GBM) is the most aggressive brain cancer and its relapse after surgery, chemo and radiotherapy appears to be led by GBM stem cells (GSCs). Also, tumor networking and intercellular communication play a major role in driving GBM therapy-resistance. Tunneling Nanotubes (TNTs), thin membranous open-ended channels connecting distant cells, have been observed in several types of cancer, where
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Loss of cell wall integrity genes cpxA and mrcB causes flocculation in Escherichia coli Biochem. J. (IF 4.097) Pub Date : 2021-01-15 Sugawara, Keita; Toyoda, Hayato; Kimura, Mami; Hayasaka, Shunsuke; Saito, Hiromi; Kobayashi, Hiroshi; Ihara, Kunio; Ida, Tomoaki; Akaike, Takaaki; Ando, Eiji; Hyodo, Mamoru; Hayakawa, Yoshihiro; Hamamoto, Shin; Uozumi, Nobuyuki
Flocculation has been recognized for hundreds of years as an important phenomenon in brewing and wastewater treatment. However, the underlying molecular mechanisms remain elusive. The lack of a distinct phenotype to differentiate between slow-growing mutants and floc-forming mutants prevents the isolation of floc-related gene by conventional mutant screening. To overcome this, we performed a two-step
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Multistep optimization of a cell-penetrating peptide towards its antimicrobial activity Biochem. J. (IF 4.097) Pub Date : 2021-01-15 Drexelius, Marco; Reinhardt, Andre; Grabeck, Joshua; Cronenberg, Tom; Nitsche, Frank; Huesgen, Pitter F.; Maier, Berenike; Neundorf, Ines
Multidrug resistant (MDR) bacteria have adapted to most clinical antibiotics and are a growing threat to human health. One promising type of candidates for the everlasting demand of new antibiotic compounds constitute antimicrobial peptides (AMPs). These peptides act against different types of microbes by permeabilizing pathogen cell membranes, whereas being harmless to mammalian cells. Contrarily
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A new function for the xanthophyll zeaxanthin: glueing chlorophyll biosynthesis to thylakoid protein assembly Biochem. J. (IF 4.097) Pub Date : 2021-01-15 Bassi, Roberto
Xanthophylls are coloured isoprenoid metabolites synthesized in many organisms with a variety of functions from the attraction of animals for impollination to absorption of light energy for photosynthesis to photoprotection against photooxidative stress. The finding by Proctor and co-workers makes a new addition to the last type of functions by showing that zeaxanthin is instrumental in coordinating
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Elucidation of an essential function of the unique charged domain of Plasmodium topoisomerase III Biochem. J. (IF 4.097) Pub Date : 2020-12-23 Bansod, Shephali; Bung, Navneet; Singh, Priyanka; Suthram, Niranjan; Choudhury, Himashree; Roy, Arijit; Bulusu, Gopalakrishnan; Bhattacharyya, Sunanda
Topoisomerase III (TopoIII) along with RecQ helicases are required for the resolution of abnormal DNA structures that result from the stalling of replication forks. Sequence analyses have identified a putative TopoIII in the Plasmodium falciparum genome (PfTopoIII). PfTopoIII shows dual nuclear and mitochondrial localization. The expression and association of PfTopoIII with mtDNA are tightly linked
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Crystal structure of human APPL BAR-PH heterodimer reveals a flexible dimeric BAR curve: implication in mutual regulation of endosomal targeting Biochem. J. (IF 4.097) Pub Date : 2020-12-23 Chen, Yujie; Zhang, Wen; Chen, Bin; Liu, Ying; Dong, Yuhui; Xu, Aimin; Hao, Quan
The APPL (adaptor proteins containing pleckstrin homology domain, phosphotyrosine binding domain and a leucine zipper motif) family consists of two isoforms, APPL1 and APPL2. By binding to curved plasma membrane, these adaptor proteins associate with multiple transmembrane receptors and recruit various downstream signaling components. They are involved in the regulation of signaling pathways evoked
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The Arabidopsis locus AT3G03890 encodes a dimeric β-barrel protein implicated in heme degradation Biochem. J. (IF 4.097) Pub Date : 2020-12-23 Wang, Jia; Guo, Qi; Li, Xiaoyi; Wang, Xiao; Liu, Lin
Plant tetrapyrroles, including heme and bilins, are synthesized in plastids. Heme oxygenase (HO) catalyzes the oxidative cleavage of heme to the linear tetrapyrrole biliverdin as the initial step in bilin biosynthesis. Besides the canonical α-helical HO that is conserved from prokaryotes to human, a subfamily of non-canonical dimeric β-barrel HO has been found in bacteria. In this work, we discovered
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Structural insights into the bypass of the major deaminated purines by translesion synthesis DNA polymerase Biochem. J. (IF 4.097) Pub Date : 2020-12-23 Jung, Hunmin; Hawkins, Michael A.; Lee, Seongmin
The exocyclic amines of nucleobases can undergo deamination by various DNA damaging agents such as reactive oxygen species, nitric oxide, and water. The deamination of guanine and adenine generates the promutagenic xanthine and hypoxanthine, respectively. The exocyclic amines of bases in DNA are hydrogen bond donors, while the carbonyl moiety generated by the base deamination acts as hydrogen bond
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Correction: Human acyl-CoA:cholesterol acyltransferase 2 gene expression in intestinal Caco-2 cells and in hepatocellular carcinoma Biochem. J. (IF 4.097) Pub Date : 2020-12-23 Song, Bao-Liang; Wang, Can-Hua; Yao, Xiao-Min; Yang, Li; Zhang, Wen-Jing; Wang, Zhen-Zhen; Zhao, Xiao-Nan; Yang, Jin-Bo; Qi, Wei; Yang, Xin-Ying; Inoue, Kenji; Lin, Zhi-Xin; Zhang, Hui-Zhan; Kodama, Tatsuhiko; Chang, Catherine C.Y.; Liu, Yin-Kun; Chang, Ta-Yuan; Li, Bo-Liang
Biochem. J. (2006) 394: 617–626. DOI: https://doi.org/10.1042/BJ20051417The authors of the original article ‘Human acyl-CoA:cholesterol acyltransferase 2 gene expression in intestinal Caco-2 cells and in hepatocellular carcinoma’ (Biochemical Journal [2006] 394[3], DOI:10.1042/BJ20051417) would like to address concerns raised by a reader regarding the duplication of loading controls in Figures 4D,
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Correction: DJ-1 interacts with RACK1 and protects neurons from oxidative-stress-induced apoptosis Biochem. J. (IF 4.097) Pub Date : 2020-12-23 Ma, Jun; Wu, Rong; Zhang, Qiang; Wu, Jun-bing; Lou, Jizhong; Zheng, Zheng; Ding, Jian-qing; Yuan, Zengqiang
Biochem. J. (2014) 462(3): 489–497. https://doi.org/10.1042/BJ20140235In this article (Biochem. J. 2014, 462, 489–497), which appeared in the Sep 15, 2014 issue of Biochemical Journal (1), the loading control in Figure 2C was inadvertently duplicated from the IgG of Figure 2D during the assembly of the figure. The authors reviewed the original scans and found the correct Western blots of the loading
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2′,7′-dichlorofluorescin-based analysis of Fenton chemistry reveals auto-amplification of probe fluorescence and albumin as catalyst for the detection of hydrogen peroxide Biochem. J. (IF 4.097) Pub Date : 2020-12-23 Gonzalez, Teresa; Peiretti, Franck; Defoort, Catherine; Borel, Patrick; Govers, Roland
Fluorophore 2′,7′-dichlorofluorescin (DCF) is the most frequently used probe for measuring oxidative stress in cells, but many aspects of DCF remain to be revealed. Here, DCF was used to study the Fenton reaction in detail, which confirmed that in a cell-free system, the hydroxyl radical was easily measured by DCF, accompanied by the consumption of H2O2 and the conversion of ferrous iron into ferric
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Interrogation of 3D-swapped structure and functional attributes of quintessential Sortase A from Streptococcus pneumoniae Biochem. J. (IF 4.097) Pub Date : 2020-12-23 Biswas, Tora; Misra, Anurag; Das, Sreetama; Yadav, Prity; Ramakumar, Suryanarayanarao; Roy, Rajendra P.
The anchoring of the surface proteins to the cell wall in gram-positive bacteria involves a peptide ligation reaction catalyzed by transpeptidase sortase. Most bacterial genomes encode multiple sortases with dedicated functions. Streptococcus pneumoniae (Sp) carries four sortases; a housekeeping sortase (SrtA), and three pilin specific sortases (SrtC1, C2, C3) dedicated to the biosynthesis of covalent
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Abnormal sterol-induced cell wall glucan deficiency in yeast is due to impaired glucan synthase transport to the plasma membrane Biochem. J. (IF 4.097) Pub Date : 2020-12-23 Gutierrez-Armijos, L. Roxana; Sussmann, Rodrigo A. C.; Silber, Ariel M.; Cortez, Mauro; Hernández, Agustín
Abnormal sterols disrupt cellular functions through yet unclear mechanisms. In Saccharomyces cerevisiae, accumulation of Δ8-sterols, the same type of sterols observed in patients of Conradi–Hünermann–Happle syndrome or in fungi after amine fungicide treatment, leads to cell wall weakness. We have studied the influence of Δ8-sterols on the activity of glucan synthase I, the protein synthetizing the
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Functions and regulation of the serine/threonine protein kinase CK1 family: moving beyond promiscuity Biochem. J. (IF 4.097) Pub Date : 2020-12-11 Fulcher, Luke J.; Sapkota, Gopal P.
Regarded as constitutively active enzymes, known to participate in many, diverse biological processes, the intracellular regulation bestowed on the CK1 family of serine/threonine protein kinases is critically important, yet poorly understood. Here, we provide an overview of the known CK1-dependent cellular functions and review the emerging roles of CK1-regulating proteins in these processes. We go
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Structure of the FERM domain of a neural scaffold protein FRMPD4 implicated in X-linked intellectual disability Biochem. J. (IF 4.097) Pub Date : 2020-12-11 Wang, Mengli; Lin, Lin; Shi, Yingdong; He, Liping; Wang, Chao; Zhu, Jinwei
Scaffold proteins play crucial roles in orchestrating synaptic signaling and plasticity in the excitatory synapses by providing a structural link between glutamatergic receptors, signaling molecules, and neuronal cytoskeletons. FRMPD4 is a neural scaffold protein that binds to metabotropic glutamate receptors via its FERM domain. Here, we determine the crystal structure of the FERM domain of FRMPD4
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Mg-protoporphyrin IX monomethyl ester cyclase from Rhodobacter capsulatus: radical SAM-dependent synthesis of the isocyclic ring of bacteriochlorophylls Biochem. J. (IF 4.097) Pub Date : 2020-12-11 Wiesselmann, Milan; Hebecker, Stefanie; Borrero-de Acuña, José M.; Nimtz, Manfred; Bollivar, David; Jänsch, Lothar; Moser, Jürgen; Jahn, Dieter
During bacteriochlorophyll a biosynthesis, the oxygen-independent conversion of Mg-protoporphyrin IX monomethyl ester (Mg-PME) to protochlorophyllide (Pchlide) is catalyzed by the anaerobic Mg-PME cyclase termed BchE. Bioinformatics analyses in combination with pigment studies of cobalamin-requiring Rhodobacter capsulatus mutants indicated an unusual radical S-adenosylmethionine (SAM) and cobalamin-dependent
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Modified organophosphorus fire retardant with low toxicity/high flame retardancy using the pharmacophore model associated with Mamdani fuzzy inference approach Biochem. J. (IF 4.097) Pub Date : 2020-12-11 Yang, Jiawen; Hou, Yilin; Li, Qing; Li, Yu
The bi-directional selective low toxicity/high flame retardancy organophosphorus fire retardants (OPFRs) derivatives were designed by a comprehensive effect 3D quantitative structure-activity relationship (QSAR) pharmacophore model, and the toxicity and flame retardancy mechanism of OPFR derivatives were explored. The 3D-QSAR comprehensive pharmacophore model was constructed using the toxicity/flame
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Impairing activation of phospholipid synthesis by c-Fos interferes with glioblastoma cell proliferation Biochem. J. (IF 4.097) Pub Date : 2020-12-11 Prucca, César G.; Racca, Ana C.; Velazquez, Fabiola N.; Cardozo Gizzi, Andrés M.; Rodríguez Berdini, Lucia; Caputto, Beatriz L.
Glioblastoma multiforme is the most aggressive type of tumor of the CNS with an overall survival rate of approximately one year. Since this rate has not changed significantly over the last 20 years, the development of new therapeutic strategies for the treatment of these tumors is peremptory. The over-expression of the proto-oncogene c-Fos has been observed in several CNS tumors including glioblastoma
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Deep learning and generative methods in cheminformatics and chemical biology: navigating small molecule space intelligently Biochem. J. (IF 4.097) Pub Date : 2020-12-11 Kell, Douglas B.; Samanta, Soumitra; Swainston, Neil
The number of ‘small’ molecules that may be of interest to chemical biologists — chemical space — is enormous, but the fraction that have ever been made is tiny. Most strategies are discriminative, i.e. have involved ‘forward’ problems (have molecule, establish properties). However, we normally wish to solve the much harder generative or inverse problem (describe desired properties, find molecule)
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Amyloid-beta oligomers induce Parkin-mediated mitophagy by reducing Miro1 Biochem. J. (IF 4.097) Pub Date : 2020-12-11 Kam, Min Kyoung; Lee, Dong Gil; Kim, Bokyung; Huh, Jae-Won; Lee, Hong Jun; Park, Young-Ho; Lee, Dong-Seok
Alzheimer's disease (AD) is a neurodegenerative disease associated with the accumulation of amyloid-beta oligomers (AβO). Recent studies have demonstrated that mitochondria-specific autophagy (mitophagy) contributes to mitochondrial quality control by selectively eliminating the dysfunctional mitochondria. Mitochondria motility, which is regulated by Miro1, is also associated with neuronal cell functions
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Correction: Effects of PKB/Akt inhibitors on insulin-stimulated lipogenesis and phosphorylation state of lipogenic enzymes in white adipose tissue Biochem. J. (IF 4.097) Pub Date : 2020-12-11 Hussain, Nusrat; Chuang, Sheng-Ju; Johanns, Manuel; Vertommen, Didier; Steinberg, Gregory R.; Kemp, Bruce E.; Rider, Mark H.
Biochem J (2020) 477 (8): 1373–1389 https://doi.org/10.1042/BCJ20190788During the production process the Western blots for pThr246 PRAS40 in Figure 6B were accidentally duplicated in Figure 6C pThr649 AS160. Portland Press apologises for any confusion caused by this. The correct version of Figure 6 can be viewed below.The y-axes of Figure 8A and 8B should be labelled ‘Rate of lipogenesis (nmol of [U-14C]
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Methylation of two-component response regulator MtrA in mycobacteria negatively modulates its DNA binding and transcriptional activation Biochem. J. (IF 4.097) Pub Date : 2020-12-11 Singhal, Anshika; Virmani, Richa; Naz, Saba; Arora, Gunjan; Gaur, Mohita; Kundu, Parijat; Sajid, Andaleeb; Misra, Richa; Dabla, Ankita; Kumar, Suresh; Nellissery, Jacob; Molle, Virginie; Gerth, Ulf; Swaroop, Anand; Sharma, Kirti; Nandicoori, Vinay K.; Singh, Yogendra
Post-translational modifications such as phosphorylation, nitrosylation, and pupylation modulate multiple cellular processes in Mycobacterium tuberculosis. While protein methylation at lysine and arginine residues is widespread in eukaryotes, to date only two methylated proteins in Mtb have been identified. Here, we report the identification of methylation at lysine and/or arginine residues in nine
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PARP-1 activation after oxidative insult promotes energy stress-dependent phosphorylation of YAP1 and reduces cell viability Biochem. J. (IF 4.097) Pub Date : 2020-12-11 Martín-Guerrero, Sandra M.; Casado, Pedro; Hijazi, Maruan; Rajeeve, Vinothini; Plaza-Díaz, Julio; Abadía-Molina, Francisco; Navascués, Julio; Cuadros, Miguel A.; Cutillas, Pedro R.; Martín-Oliva, David
Poly(ADP-ribose) polymerase 1 (PARP-1) is a nuclear enzyme that catalyze the transfer of ADP-ribose units from NAD+ to several target proteins involved in cellular stress responses. Using WRL68 (HeLa derivate) cells, we previously showed that PARP-1 activation induced by oxidative stress after H2O2 treatment lead to depletion of cellular NAD+ and ATP, which promoted cell death. In this work, LC–MS/MS-based
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The biophysical basis of receptor tyrosine kinase ligand functional selectivity: Trk-B case study Biochem. J. (IF 4.097) Pub Date : 2020-12-11 Ahmed, Fozia; Paul, Michael D.; Hristova, Kalina
Tropomyosin receptor kinase B (Trk-B) belongs to the second largest family of membrane receptors, Receptor Tyrosine Kinases (RTKs). Trk-B is known to interact with three different neurotrophins: Brain-Derived Neurotrophic Factor (BDNF), Neurotrophin-4 (NT-4), and Neurotrophin-3 (NT-3). All three neurotrophins are involved in survival and proliferation of neuronal cells, but each induces distinct signaling
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Crystal structures of ORFV125 provide insight into orf virus-mediated inhibition of apoptosis Biochem. J. (IF 4.097) Pub Date : 2020-12-11 Suraweera, Chathura D.; Hinds, Mark G.; Kvansakul, Marc
Premature apoptosis of cells is a strategy utilized by multicellular organisms to counter microbial threats. Orf virus (ORFV) is a large double-stranded DNA virus belonging to the poxviridae. ORFV encodes for an apoptosis inhibitory protein ORFV125 homologous to B-cell lymphoma 2 or Bcl-2 family proteins, which has been shown to inhibit host cell encoded pro-apoptotic Bcl-2 proteins. However, the structural
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Translesion synthesis of the major nitrogen mustard-induced DNA lesion by human DNA polymerase η Biochem. J. (IF 4.097) Pub Date : 2020-12-11 Jung, Hummin; Rayala, Naveen Kumar; Lee, Seongmin
Nitrogen mustards are among the first modern anticancer chemotherapeutics that are still widely used as non-specific anticancer alkylating agents. While the mechanism of action of mustard drugs involves the generation of DNA interstrand cross-links, the predominant lesions produced by these drugs are nitrogen half-mustard-N7-dG (NHMG) adducts. The bulky major groove lesion NHMG, if left unrepaired
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PROTEIN l-ISOASPARTYL METHYLTRANSFERASE (PIMT) in plants: regulations and functions Biochem. J. (IF 4.097) Pub Date : 2020-11-27 Kamble, Nitin Uttam; Majee, Manoj
Proteins are essential molecules that carry out key functions in a cell. However, as a result of aging or stressful environments, the protein undergoes a range of spontaneous covalent modifications, including the formation of abnormal l-isoaspartyl residues from aspartyl or asparaginyl residues, which can disrupt the protein's inherent structure and function. PROTEIN l-ISOASPARTYL METHYLTRANSFERASE
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Endogenous Rab29 does not impact basal or stimulated LRRK2 pathway activity Biochem. J. (IF 4.097) Pub Date : 2020-11-27 Kalogeropulou, Alexia F.; Freemantle, Jordana B.; Lis, Pawel; Vides, Edmundo G.; Polinski, Nicole K.; Alessi, Dario R.
Mutations that enhance LRRK2 protein kinase activity cause inherited Parkinson's disease. LRRK2 phosphorylates a group of Rab GTPase proteins, including Rab10 and Rab12, within the effector-binding switch-II motif. Previous work has indicated that the PARK16 locus, which harbors the gene encoding for Rab29, is involved in Parkinson's, and that Rab29 operates in a common pathway with LRRK2. Co-expression
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Biochemical and transcript level differences between the three human phosphofructokinases show optimisation of each isoform for specific metabolic niches Biochem. J. (IF 4.097) Pub Date : 2020-11-27 Fernandes, Peter M.; Kinkead, James; McNae, Iain; Michels, Paul A.M.; Walkinshaw, Malcolm D.
6-Phosphofructokinase-1-kinase (PFK) tetramers catalyse the phosphorylation of fructose 6-phosphate (F6P) to fructose 1,6-bisphosphate (F16BP). Vertebrates have three PFK isoforms (PFK-M, PFK-L, and PFK-P). This study is the first to compare the kinetics, structures, and transcript levels of recombinant human PFK isoforms. Under the conditions tested PFK-M has the highest affinities for F6P and ATP
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A-loop interactions in Mer tyrosine kinase give rise to inhibitors with two-step mechanism and long residence time of binding Biochem. J. (IF 4.097) Pub Date : 2020-11-27 Pflug, Alexander; Schimpl, Marianne; Nissink, J. Willem M.; Overman, Ross C.; Rawlins, Philip B.; Truman, Caroline; Underwood, Elizabeth; Warwicker, Juli; Winter-Holt, Jon; McCoull, William
The activation loop (A-loop) plays a key role in regulating the catalytic activity of protein kinases. Phosphorylation in this region enhances the phosphoryl transfer rate of the kinase domain and increases its affinity for ATP. Furthermore, the A-loop possesses autoinhibitory functions in some kinases, where it collapses onto the protein surface and blocks substrate binding when unphosphorylated.
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Phosphoinositide 3-kinases in platelets, thrombosis and therapeutics Biochem. J. (IF 4.097) Pub Date : 2020-11-27 Ribes, Agnès; Oprescu, Antoine; Viaud, Julien; Hnia, Karim; Chicanne, Gaëtan; Xuereb, Jean-Marie; Severin, Sonia; Gratacap, Marie-Pierre; Payrastre, Bernard
Our knowledge on the expression, regulation and roles of the different phosphoinositide 3-kinases (PI3Ks) in platelet signaling and functions has greatly expanded these last twenty years. Much progress has been made in understanding the roles and regulations of class I PI3Ks which produce the lipid second messenger phosphatidylinositol 3,4,5 trisphosphate (PtdIns(3,4,5)P3). Selective pharmacological
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Another twist to the GLI code Biochem. J. (IF 4.097) Pub Date : 2020-11-27 Timmis, Alex J.; Riobo-Del Galdo, Natalia A.
The canonical Hedgehog (Hh) signalling pathway is essential for vertebrate development and its uncontrolled activation is a common occurrence in human cancers. Hh signalling converges in the modification of a family of transcription factors, GLI1, GLI2 and GLI3, to orchestrate a cell type and context-specific transcriptional response. Despite binding to very similar responsive elements, the GLI family
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Insights into the regulation of the matriptase-prostasin proteolytic system Biochem. J. (IF 4.097) Pub Date : 2020-11-27 Holt-Danborg, Lasse; Skovbjerg, Signe; Goderum, Kristian W.; Nonboe, Annika W.; Stankevic, Evelina; Frost, Ásdis K.; Vitved, Lars; Jensen, Jan K.; Vogel, Lotte K.
The membrane-associated prostasin and matriptase belonging to the S1A subfamily of serine proteases, are critical for epithelial development and maintenance. The two proteases are involved in the activation of each other and are both regulated by the protease inhibitors, HAI-1 and HAI-2. The S1A subfamily of serine proteases are generally produced as inactive zymogens requiring a cleavage event to
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eEF2K enhances expression of PD-L1 by promoting the translation of its mRNA Biochem. J. (IF 4.097) Pub Date : 2020-11-27 Wu, Yu; Xie, Jianling; Jin, Xin; Lenchine, Roman V.; Wang, Xuemin; Fang, Danielle M.; Nassar, Zeyad D.; Butler, Lisa M.; Li, Jing; Proud, Christopher G.
Emerging advances in cancer therapy have transformed the landscape towards cancer immunotherapy regimens. Recent discoveries have resulted in the development of clinical immune checkpoint inhibitors that are ‘game-changers’ for cancer immunotherapy. Here we show that eEF2K, an atypical protein kinase that negatively modulates the elongation stage of protein synthesis, promotes the synthesis of PD-L1
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Fragment-derived modulators of an industrial β-glucosidase Biochem. J. (IF 4.097) Pub Date : 2020-11-27 Makraki, Eleni; Darby, John F.; Carneiro, Marta G.; Firth, James D.; Heyam, Alex; AB, Eiso; O'Brien, Peter; Siegal, Gregg; Hubbard, Roderick E.
A fragment screen of a library of 560 commercially available fragments using a kinetic assay identified a small molecule that increased the activity of the fungal glycoside hydrolase TrBgl2. An analogue by catalogue approach and detailed kinetic analysis identified improved compounds that behaved as nonessential activators with up to a 2-fold increase in maximum activation. The compounds did not activate
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Structure, metabolism and biological functions of steryl glycosides in mammals Biochem. J. (IF 4.097) Pub Date : 2020-11-13 Shimamura, Michio
Steryl glycosides (SGs) are sterols glycosylated at their 3β-hydroxy group. They are widely distributed in plants, algae, and fungi, but are relatively rare in bacteria and animals. Glycosylation of sterols, resulting in important components of the cell membrane SGs, alters their biophysical properties and confers resistance against stress by freezing or heat shock to cells. Besides, many biological
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Identification of a glycan cluster in gp120 essential for irreversible HIV-1 lytic inactivation by a lectin-based recombinantly engineered protein conjugate Biochem. J. (IF 4.097) Pub Date : 2020-11-13 Parajuli, Bibek; Acharya, Kriti; Nangarlia, Aakansha; Zhang, Shiyu; Parajuli, Bijay; Dick, Alexej; Ngo, Brendon; Abrams, Cameron F.; Chaiken, Irwin
We previously discovered a class of recombinant lectin conjugates, denoted lectin DLIs (‘dual-acting lytic inhibitors’) that bind to the HIV-1 envelope (Env) protein trimer and cause both lytic inactivation of HIV-1 virions and cytotoxicity of Env-expressing cells. To facilitate mechanistic investigation of DLI function, we derived the simplified prototype microvirin (MVN)-DLI, containing an MVN domain
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Phospholamban and sarcolipin prevent thermal inactivation of sarco(endo)plasmic reticulum Ca2+-ATPases Biochem. J. (IF 4.097) Pub Date : 2020-11-13 Fu, Minghua; Bombardier, Eric; Gamu, Daniel; Tupling, A. Russell
Na+-K+-ATPase from mice lacking the γ subunit exhibits decreased thermal stability. Phospholamban (PLN) and sarcolipin (SLN) are small homologous proteins that regulate sarco(endo)plasmic reticulum Ca2+-ATPases (SERCAs) with properties similar to the γ subunit, through physical interactions with SERCAs. Here, we tested the hypothesis that PLN and SLN may protect against thermal inactivation of SERCAs
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Domain interactions reveal auto-inhibition of the deubiquitinating enzyme USP19 and its activation by HSP90 in the modulation of huntingtin aggregation Biochem. J. (IF 4.097) Pub Date : 2020-11-13 Xue, Wei; Zhang, Shu-Xian; He, Wen-Tian; Hong, Jun-Ye; Jiang, Lei-Lei; Hu, Hong-Yu
Ubiquitin-specific protease 19 (USP19) is a member of the deubiquitinating (DUB) enzymes that catalyze removing the ubiquitin signals from target proteins. Our previous research has demonstrated that USP19 up-regulates the protein level and aggregation of polyQ-expanded huntingtin through the involvement of heat shock protein 90 (HSP90). Here, we present solution structures of the CS1, CS2 and UbL
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Crystal structure of Leptospira leucine-rich repeat 20 reveals a novel E-cadherin binding protein to induce NGAL expression in HK2 cells Biochem. J. (IF 4.097) Pub Date : 2020-11-13 Hsu, Shen-Hsing; Chu, Chen-Hsi; Tian, Ya-Chung; Chang, Ming-Yang; Chou, Li-Feng; Sun, Yuh-Ju; Yang, Chih-Wei
Leptospirosis is the most common zoonotic disease caused by pathogenic Leptospira, which is classified into three groups according to virulence. Its pathogenic and intermediate species contain leucine-rich repeat (LRR) proteins that are rarely expressed in non-pathogenic strains. In this study, we presented the crystal structure of LSS_11580 (rLRR20) from pathogenic L. santarosai serovar Shermani.
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Structure-based drug repurposing to inhibit the DNA gyrase of Mycobacterium tuberculosis Biochem. J. (IF 4.097) Pub Date : 2020-11-13 GL, Balasubramani; Rajput, Rinky; Gupta, Manish; Dahiya, Pradeep; Thakur, Jitendra K.; Bhatnagar, Rakesh; Grover, Abhinav
Drug repurposing is an alternative avenue for identifying new drugs to treat tuberculosis (TB). Despite the broad-range of anti-tubercular drugs, the emergence of multi-drug-resistant and extensively drug-resistant strains of Mycobacterium tuberculosis (Mtb) H37Rv, as well as the significant death toll globally, necessitates the development of new and effective drugs to treat TB. In this study, we
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Transporter tandems: precise tools for normalizing active transporter in the plasma membrane Biochem. J. (IF 4.097) Pub Date : 2020-11-13 Tschirka, Julia; Bach, Markus; Kisis, Ilmars; Lemmen, Julia; Gnoth, Mark Jean; Gründemann, Dirk
The transport efficiency (TE) describes the performance of a transport protein for a specific substrate. To compare the TE of different transporters, the number of active transporters in the plasma membrane must be monitored, as it may vary for each transporter and experiment. Available methods, like LC–MS quantification of tryptic peptides, fail to discriminate inactive intracellular transporters
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Conserved roles for receptor tyrosine kinase extracellular regions in regulating receptor and pathway activity Biochem. J. (IF 4.097) Pub Date : 2020-11-13 Gonzalez-Magaldi, Monica; McCabe, Jacqueline M.; Cartwright, Haley N.; Sun, Ningze; Leahy, Daniel J.
Receptor Tyrosine Kinases (RTKs) comprise a diverse group of cell-surface receptors that mediate key signaling events during animal development and are frequently activated in cancer. We show here that deletion of the extracellular regions of 10 RTKs representing 7 RTK classes or their substitution with the dimeric immunoglobulin Fc region results in constitutive receptor phosphorylation but fails
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Identification of an l-serine/l-threonine dehydratase with glutamate racemase activity in mammals Biochem. J. (IF 4.097) Pub Date : 2020-11-13 Katane, Masumi; Nakasako, Kento; Yako, Kanato; Saitoh, Yasuaki; Sekine, Masae; Homma, Hiroshi
Recent investigations have shown that multiple d-amino acids are present in mammals and these compounds have distinctive physiological functions. Free d-glutamate is present in various mammalian tissues and cells and in particular, it is presumably correlated with cardiac function, and much interest is growing in its unique metabolic pathways. Recently, we first identified d-glutamate cyclase as its
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Blackout in the powerhouse: clinical phenotypes associated with defects in the assembly of OXPHOS complexes and the mitoribosome Biochem. J. (IF 4.097) Pub Date : 2020-11-13 Hock, Daniella H.; Robinson, David R. L.; Stroud, David A.
Mitochondria produce the bulk of the energy used by almost all eukaryotic cells through oxidative phosphorylation (OXPHOS) which occurs on the four complexes of the respiratory chain and the F1–F0 ATPase. Mitochondrial diseases are a heterogenous group of conditions affecting OXPHOS, either directly through mutation of genes encoding subunits of OXPHOS complexes, or indirectly through mutations in
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Structural insight into the catalytic mechanism and inhibitor binding of aminopeptidase A Biochem. J. (IF 4.097) Pub Date : 2020-11-13 Couvineau, Pierre; De Almeida, Hugo; Leroux, Vincent; Roques, Bernard; Maigret, Bernard; Llorens-Cortes, Catherine; Iturrioz, Xavier
Aminopeptidase A (APA) is a membrane-bound monozinc aminopeptidase. In the brain, APA generates angiotensin III which exerts a tonic stimulatory effect on the control of blood pressure (BP) in hypertensive animals. The oral administration of RB150 renamed firibastat by WHO, an APA inhibitor prodrug, targeting only the S1 subsite, decreases BP in hypertensive patients from various ethnic origins. To
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Functional analysis of a species-specific inhibitor selective for human Na+-coupled citrate transporter (NaCT/SLC13A5/mINDY) Biochem. J. (IF 4.097) Pub Date : 2020-11-13 Higuchi, Kei; Kopel, Jonathan J.; Sivaprakasam, Sathish; Jaramillo-Martinez, Valeria; Sutton, R. Bryan; Urbatsch, Ina L.; Ganapathy, Vadivel
The Na+-coupled citrate transporter (NaCT/SLC13A5/mINDY) in the liver delivers citrate from the blood into hepatocytes. As citrate is a key metabolite and regulator of multiple biochemical pathways, deletion of Slc13a5 in mice protects against diet-induced obesity, diabetes, and metabolic syndrome. Silencing the transporter suppresses hepatocellular carcinoma. Therefore, selective blockers of NaCT
更新日期:2020-11-05