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Biochemical Journal

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https://www.readbyqxmd.com/read/30642888/the-transmembrane-autophagy-cargo-receptors-ati1-and-ati2-interact-with-atg8-through-intrinsically-disordered-regions-with-distinct-biophysical-properties
#1
Ida Marie Zobbe Sjøgaard, Simon Bressendorff, Andreas Prestel, Swathi Kausika, Emilie Oksbjerg, Birthe B Kragelund, Peter Brodersen
Selective autophagy has emerged as an important mechanism by which eukaryotic cells control the abundance of specific proteins. This mechanism relies on cargo recruitment to autophagosomes by receptors that bind to both the ubiquitin-like AUTOPHAGY8 (ATG8) protein through ATG8 interacting motifs (AIMs) and to the cargo to be degraded. In plants, two autophagy cargo receptors, ATG8 Interacting Protein 1 (ATI1) and 2 (ATI2), were identified early on, but their molecular properties remain poorly understood. Here, we show that ATI1 and ATI2 are transmembrane proteins with long N-terminal intrinsically disordered regions (IDRs)...
January 14, 2019: Biochemical Journal
https://www.readbyqxmd.com/read/30635360/high-intensity-exercise-inhibits-carnitine-palmitoyltransferase-i-sensitivity-to-l-carnitine
#2
Heather L Petrick, Graham P Holloway
The decline in fat oxidation at higher power outputs of exercise is a complex interaction between several mechanisms, however the influence of mitochondrial bioenergetics in this process remains elusive. Therefore, using permeabilized muscle fibers from mouse skeletal muscle, we aimed to determine if acute exercise altered mitochondrial sensitivity to 1) adenosine diphosphate (ADP) and inorganic phosphate (Pi), or 2) carnitine palmitoyltransferase-I (CPT-I) independent (palmitoylcarnitine, PC) and dependent (palmitoyl-CoA (P-CoA), malonyl-CoA (M-CoA), and L-carnitine) substrates, in an intensity-dependent manner...
January 11, 2019: Biochemical Journal
https://www.readbyqxmd.com/read/30635359/niclosamide-induced-wnt-signaling-inhibition-in-colorectal-cancer-is-mediated-by-autophagy
#3
Jiangbo Wang, Xiu-Rong Ren, Hailan Piao, Shengli Zhao, Takuya Osada, Richard T Premont, Robert A Mook, Michael A Morse, Herbert Kim Lyerly, Wei Chen
The Wnt signaling pathway, known for regulating genes critical to normal embryonic development and tissue homeostasis, is dysregulated in many types of cancer. Previously we identified that the anthelmintic drug niclosamide inhibited  Wnt signaling by promoting internalization of Wnt receptor Frizzled 1 and degradation of  Wnt signaling pathway proteins Dishevelled 2 and β-catenin, contributing to suppression of colorectal cancer growth in vitro and in vivo   Here we provide evidence that niclosamide-mediated inhibition of Wnt signaling is mediated through autophagosomes induced by niclosamide...
January 11, 2019: Biochemical Journal
https://www.readbyqxmd.com/read/30626614/endothelin-converting-enzyme-1-regulates-glucagon-like-peptide-1-receptor-signalling-and-resensitisation
#4
Gary Brian Willars, Jing Lu
Following nutrient ingestion, glucagon-like peptide 1 (GLP-1) is secreted from intestinal L-cells and mediates anti-diabetic effects, most notably stimulating glucose-dependent insulin release from pancreatic β-cells but also inhibiting glucagon release, promoting satiety and weight reduction and potentially enhancing or preserving β-cell mass.  These effects are mediated by the GLP-1 receptor (GLP-1R) which is a therapeutic target in type 2 diabetes.  Although agonism at the GLP-1R has been well-studied, desensitisation and resensitisation are perhaps less well explored...
January 9, 2019: Biochemical Journal
https://www.readbyqxmd.com/read/30626613/solution-structure-of-tbtfiis2-2-pwwp-domain-from-trypanosoma-brucei-and-its-binding-to-h4k17me3-and-h3k32me3
#5
Rui Wang, Jie Gao, Jiahai Zhang, Xuecheng Zhang, Chao Xu, Shanhui Liao, Xiaoming Tu
Posttranslational modifications (PTMs) of core histones, such as histone methylation, play critical roles in a variety of biological processes including transcription regulation, chromatin condensation and DNA repair. In T. brucei , no domain recognizing methylated histone has been identified so far. TbTFIIS2-2, as a potential transcription elongation factors in T. brucei , contains a PWWP domain in the N-terminus which shares low sequence similarity compared with other PWWP domains and is absent in other TFIIS factors ...
January 9, 2019: Biochemical Journal
https://www.readbyqxmd.com/read/30622151/identification-of-substrate-specific-inhibitors-of-cathepsin-k-through-high-throughput-screening
#6
Simon Law, Xin Du, Preety Panwar, Nicolette S Honson, Tom Pfeifer, Michel Roberge, Dieter Brömme
Cathepsin K (CatK) is a cysteine protease and drug target for skeletal disorders that is known for its potent collagenase and elastase activity. The formation of oligomeric complexes of CatK in the presence of glycosaminoglycans has been associated with its collagenase activity. Inhibitors that disrupt these complexes can selectively block the collagenase activity without interfering with the other regulatory proteolytic activities of the enzyme. Here, we have developed a fluorescence polarization (FP) assay to screen 4,761 compounds for substrate specific ectosteric collagenase inhibitors of CatK...
January 8, 2019: Biochemical Journal
https://www.readbyqxmd.com/read/30617221/mov10-sequesters-the-rnp-of-influenza-a-virus-in-the-cytoplasm-and-is-antagonized-by-viral-ns1-protein
#7
Jian Li, Siqi Hu, Fengwen Xu, Shan Mei, Xiaoman Liu, Lijuan Yin, Fei Zhao, Xiaoxiao Zhao, Hong Sun, Zichen Xiong, Di Zhang, Shan Cen, Jianwei Wang, Chen Liang, Fei Guo
MOV10 has emerged as an important host antiviral factor. MOV10 not only inhibits various viruses including human immunodeficiency virus type 1, hepatitis C virus and vesicular stomatitis virus, it also restricts the activity of retroelements LINE-1, Alu, SVA and IAP. Here we report that MOV10 suppresses influenza A virus infection through interacting with viral nucleoprotein, sequestering viral RNP in the cytoplasm and causing the degradation of viral vRNA. This antiviral activity of MOV10 depends on the integrity of P-bodies...
January 7, 2019: Biochemical Journal
https://www.readbyqxmd.com/read/30610128/cga-n9-an-antimicrobial-peptide-derived-from-chromogranin-a-direct-cell-penetration-of-and-endocytosis-by-candida-tropicalis
#8
Ruifang Li, Chen Chen, Sha Zhu, Xueqin Wang, Yanhui Yang, Weini Shi, Sijia Chen, Congcong Wang, Lixing Yan, Jiaofan Shi
CGA-N9 is a peptide derived from the N-terminus of human chromogranin A comprising amino acids 47 to 55. Minimum inhibitory concentration (MIC) assays showed that CGA-N9 had antimicrobial activity and exhibited time-dependent inhibition activity against Candida tropicalis , with high safety in human red blood cells (HRBCs) and mouse brain microvascular endothelial cells (bEnd.3). According to the results of transmission electron microscopy (TEM), flow cytometry and confocal microscopy, CGA-N9 accumulated in cells without destroying the integrity of the cell membrane; the peptide was initially localized to the cell membrane and subsequently internalized into the cytosol...
January 4, 2019: Biochemical Journal
https://www.readbyqxmd.com/read/30606737/silencing-of-type-ii-phosphatidylinositol-4-kinase-%C3%AE-stabilizes-prostate-apoptosis-response-4-and-induces-apoptosis-in-cancer-cells
#9
Sonica Chaudhry, Vibhor Joshi, Naveen Bojjireddy, Maiko Thoh, Santosh Kumar Sandur, Gosukonda Subrahmanyam
Type II Phosphatidylinositol 4-kinase β (PtdIns 4-kinase II β) is an enigma among the phosphatidylinositol 4-kinase family. The role of PtdIns 4-kinase II β in MCF-7 cells was addressed with the help of short hairpin RNA (shRNA). PtdIns 4-kinase II β shRNA transfection increased pan caspase activity and induced apoptosis in cancerous MCF-7 cells.  Non-cancerous MCF-10A cells were resistant to PtdIns 4-kinase II β shRNA induced apoptosis. Caspase 8 and 9 inhibitors rescued MCF-7 cells from apoptosis. Shotgun proteomic studies with Flag-tagged PtdIns 4-kinase II β immunoprecipitates showed tumor suppressor prostate apoptosis response-4 (Par-4) as one of the interacting proteins in HEK293 cells...
January 3, 2019: Biochemical Journal
https://www.readbyqxmd.com/read/30602588/sorting-nexin-27-rescues-neuroligin-2-from-lysosomal-degradation-to-control-inhibitory-synapse-number
#10
Caroline Binda, Yasuko Nakamura, Jeremy Henley, Kevin Wilkinson
Retromer is an evolutionarily conserved endosomal trafficking complex that mediates the retrieval of cargo proteins from a degradative pathway for sorting back to the cell surface. To promote cargo recycling, the core retromer trimer of VPS26, VPS29 and VPS35 recognises cargo either directly, or through an adaptor protein, the most well-characterised of which is the PDZ domain-containing sorting nexin SNX27. Neuroligins (NLGs) are postsynaptic trans-synaptic scaffold proteins that function in the clustering of postsynaptic proteins to maintain synaptic stability...
January 2, 2019: Biochemical Journal
https://www.readbyqxmd.com/read/30602587/repurposing-of-idebenone-as-a-potential-anticancer-agent
#11
Elisabetta Damiani, Raif Yuecel, Heather M Wallace
Glioblastoma (GB) represents the most common and aggressive form of malignant primary brain tumour associated with high rates of morbidity and mortality. In this study we considered the potential use of idebenone, a Coenzyme Q10 analogue, as a novel chemotherapeutic agent for GB. On two GB cell lines, U373MG and U87MG, idebenone decreased the viable cell number and enhanced the cytotoxic effects of two known anti-proliferative agents: temozolomide and oxaliplatin. Idebenone also affected the clonogenic and migratory capacity of both GB cell lines, at 25 mM and 50 mM, a concentration equivalent to that transiently reached in plasma after oral intake that is deemed safe for humans...
January 2, 2019: Biochemical Journal
https://www.readbyqxmd.com/read/30578289/the-kh-type-splicing-regulatory-protein-ksrp-regulates-type-iii-interferon-expression-post-transcriptionally
#12
Lisa Schmidtke, Katharina Schrick, Sabrina Saurin, Rudolf Käfer, Fabian Gather, Julia Weinmann-Menke, Hartmut Kleinert, Andrea Pautz
Type III interferons (IFNs) are the latest members of the IFN family. They play an important role in immune defense mechanisms, especially in antiviral responses at mucosal sites. Moreover, they control inflammatory reactions by modulating neutrophil and dendritic cell function. Therefore, it is important to identify cellular mechanisms involved in the control of type III IFN expression. All IFN family members contain AU-rich elements (AREs) in the 3'-untranslated regions (3'-UTR) of their mRNAs that determine mRNA half-life and consequently the expressional level of these cytokines...
December 21, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/30578288/validation-of-anti-glucocerebrosidase-antibodies-for-western-blot-analysis-on-protein-lysates-of-murine-and-human-cells
#13
Wenduo Qi, Brad Davidson, Matthew Nguyen, Taylor Lindstrom, Richard J Grey, Robert Burnett, Elma Aflaki, Ellen Sidransky, Wendy Westbroek
Gaucher disease is a rare lysosomal storage disorder caused by mutations in the GBA1 gene, encoding the lysosome-resident glucocerebrosidase enzyme involved in the hydrolysis of glucosylceramide. The discovery of an association between mutations in GBA1 and the development of synucleinopathies, including Parkinson disease, has directed attention to glucocerebrosidase as a potential therapeutic target for different synucleinopathies. These findings initiated an exponential growth in research and publications regarding the glucocerebrosidase enzyme...
December 21, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/30573651/aminoglycoside-antibiotic-resistance-conferred-by-hpa2-of-mdr-a-baumannii-an-unusual-adaptation-of-a-common-histone-acetyltransferase
#14
Jyoti Singh Tomar, Rama Krishna Peddinti, Ramakrishna V Hosur
Antibiotic-resistant bacteria pose the greatest threat to human health. Among the list of such bacteria released by WHO, carbapenem-resistant Acinetobacter baumannii , for which almost no treatment exists, tops the list. A. baumannii is one of the most troublesome ESKAPE pathogens and mechanisms that have facilitated its rise as a successful pathogen are not well studied. Efforts in this direction have resulted in identification of Hpa2- Ab, an uncharacterized histone acetyltransferase enzyme of GNAT superfamily...
December 21, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/30573650/the-peroxisomal-zebrafish-scp2-thiolase-type-1-is-a-weak-transient-dimer-as-revealed-by-crystal-structures-and-native-mass-spectrometry
#15
Tiila-Riikka Kiema, Chandan J Thapa, Mikko Laitaoja, Werner Schmitz, Mirko M Maksimainen, Toshiyuki Fukao, Juha Rouvinen, Janne Jänis, Rik K Wierenga
The SCP2-thiolase (type-1) functions in the vertebrate peroxisomal, bile acid synthesis pathway, converting 24-keto-THC-CoA and CoA into choloyl-CoA and propionyl-CoA. This conversion concerns the β-oxidation chain shortening of the steroid fatty acyl moiety of 24-keto-THC-CoA. This class of dimeric thiolases has previously been poorly characterized. High resolution crystal structures of the zebrafish SCP2-thiolase (type-1) now reveal an open catalytic site, shaped by residues of both subunits. The structure of its non-dimerised monomeric form has also been captured in the obtained crystals...
December 20, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/30573649/double-trouble-gag-in-conjunction-with-double-insert-in-hiv-protease-contribute-to-reduced-drv-susceptibility
#16
Alison Williams, Adriaan Basson, Ikechukwu Achilonu, Heini W Dirr, Lynn Morris, Yasien Sayed
HIV protease is essential for processing the Gag polyprotein to produce infectious virions and is a major target in antiretroviral therapy. We have identified an unusual HIV-1 subtype C variant that contains insertions of leucine and asparagine (L38↑N↑L) in the hinge region of protease at position 38. This was isolated from a protease inhibitor naïve infant. Isothermal titration calorimetry showed that 10% less of L38↑N↑L protease was in the active conformation as compared to a reference strain. L38↑N↑L protease displayed a ±50% reduction in K M and k cat The catalytic efficiency ( k cat / K M ) of L38↑N↑L protease was not significantly different from wild-type although there was a 42% reduction of specific activity for the variant...
December 20, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/30568000/znf300-stimulates-fatty-acid-oxidation-and-alleviates-hepatosteatosis-through-regulating-ppar%C3%AE
#17
Feng Juan Yan, Yong Jian Wang, Shi Ran Yan, Jun Lu, Yuan-Lin Zheng
ZNF300 plays an important role in the regulation of HBV-related hepatocellular carcinoma. However, little is known about the role of ZNF300 in lipid metabolism and NAFLD. In the present study, we observed that ZNF300 expression was markedly decreased in free fatty acids (FFAs)-induced fatty liver. Overexpressed ZNF300 alleviated hepatic lipid accumulation, whereas knockdown of ZNF300 enhanced the FFAs-induced lipid accumulation. Investigations of the underlying mechanisms revealed that ZNF300 directly binds to and regulates the PPARα expression, thus promoting fatty acid oxidation...
December 19, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/30563945/new-structural-insights-into-anomeric-carbohydrate-recognition-by-frutalin-an-%C3%AE-d-galactose-binding-lectin-from-breadfruit-seeds
#18
Antonio Eufrasio Vieira-Neto, Felipe Domingos Sousa, Humberto M Pereira, Frederico Bruno Mendes Batista Moreno, Marcos Roberto Lourenzoni, Thalles Barbosa Grangeiro, Ana Cristina de Oliveira Monteiro-Moreira, Renato de Azevedo Moreira
Frutalin (FTL) is a multiple-binding lectin belonging to the jacalin-related-lectins (JRL) family and derived from Artocarpus incisa (breadfruit) seeds. This lectin specifically recognizes and binds α-D-galactose. FTL has been successfully used in immunobiological research for the recognition of cancer-associated oligosaccharides. However, the molecular bases by which FTL promotes these specific activities remain poorly understood. Here, we report the whole 3D structure of FTL for the first time, as determined by X-ray crystallography...
December 18, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/30563944/elevated-hypertrophy-growth-plate-maturation-glycosaminoglycan-deposition-and-exostosis-formation-in-the-hspg2-exon-3-null-mouse-intervertebral-disc
#19
Cindy C Shu, Susan M Smith, Christopher B Little, James Melrose
Heparan sulphate (HS) regulates diverse cell-signalling events in intervertebral disc development and homeostasis. The aim of the present study was to investigate the effect of ablation of perlecan-HS/CS on murine intervertebral disc development. Genetic models carrying mutations in genes encoding HS biosynthetic enzymes have identified multiple roles for HS in tissue homeostasis. In the present study we utilised an Hspg2 exon 3 null HS/CS deficient mouse to assess the role of perlecan HS in disc cell regulation...
December 18, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/30559328/engineering-arabidopsis-long-chain-acyl-coa-synthetase-9-variants-with-enhanced-enzyme-activity
#20
Yang Xu, Kristian Mark P Caldo, Roman Holic, Elzbieta Mietkiewska, Jocelyn Ozga, Syed Masood Rizvi, Guanqun Chen, Randall Weselake
Long-chain acyl-CoA synthetase (LACS, EC 6.2.1.3) catalyzes the ATP-dependent activation of free fatty acid to form acyl-CoA, which in turn serves as the major acyl donor for various lipid metabolic pathways. Increasing the size of acyl-CoA pool by enhancing LACS activity appears to be a useful approach to improve the production and modify the composition of fatty acid-derived compounds, such as triacylglycerol. In this study, we aimed to improve the enzyme activity of Arabidopsis thaliana LACS9 (AtLACS9) by introducing random mutations into its cDNA using error-prone PCR...
December 17, 2018: Biochemical Journal
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