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FEBS Journal

Nongluk Sriwilaijaroen, Shin-Ichi Nakakita, Sachiko Kondo, Hirokazu Yagi, Koichi Kato, Takeomi Murata, Hiroaki Hiramatsu, Toshio Kawahara, Yohei Watanabe, Yasushi Kanai, Takao Ono, Jun Hirabayashi, Kazuhiko Matsumoto, Yasuo Suzuki
The rapidly evolvable influenza A virus has caused pandemics linked to millions of deaths in the past century. Influenza A viruses are categorized by H (hemagglutinin; HA) and N (neuraminidase; NA) proteins expressed on the viral envelope surface. Analyses of past pandemics suggest that the HA gene segment comes from a nonhuman virus, which is then introduced into an immunologically naïve human population with potentially devastating consequences. As a prerequisite for infection, the nonhuman HA molecules of H1-H16 viruses must be able to bind to specific sialyl receptors on the host cell surface along the human respiratory tract...
March 15, 2018: FEBS Journal
Carina Strell, Markus M Hilscher, Navya Laxman, Jessica Svedlund, Chenglin Wu, Chika Yokota, Mats Nilsson
Single-cell transcriptomics provides us with completely new insights into the molecular diversity of different cell-types and the different states they can adopt. The technique generates inventories of cells that constitute the building blocks of multicellular organisms. However, since the method requires isolation of discrete cells, information about the original location within tissue is lost. Therefore, it is not possible to draw detailed cellular maps of tissue architecture and their positioning in relation to other cells...
March 14, 2018: FEBS Journal
Lei Xu, Laura J Braun, Daniel Rönnlund, Jerker Widengren, Pontus Aspenström, Annica K B Gad
Focal adhesions are subcellular regions at the micrometer scale that link the cell to the surrounding microenvironment and control vital cell functions. However, the spatial architecture of focal adhesions remains unclear at the nanometer scale. We used two-color and three-color super-resolution stimulated emission depletion microscopy to determine the spatial distributions and co-localization of endogenous focal adhesion components in fibroblasts. Our data indicate that adhesion proteins inside, but not outside, focal adhesions are organized into nanometer size units of multi-protein assemblies...
March 14, 2018: FEBS Journal
Marco Mangiagalli, Guy Sarusi, Aleksei Kaleda, Maya Bar Dolev, Valentina Nardone, Vittoria Federica Vena, Ido Braslavsky, Marina Lotti, Marco Nardini
Ice Binding Proteins (IBPs) contribute to the survival of many living beings at sub-zero temperature by controlling the formation and growth of ice crystals. This work investigates the structural basis of the ice binding properties of EfcIBP, obtained from Antarctic bacteria. EfcIBP is endowed with a unique combination of thermal hysteresis (TH) and ice recrystallization inhibition (IRI) activity. The three-dimensional structure, solved at 0.84 Å resolution, shows that EfcIBP belongs to the IBP-1 fold family, and is organized in a right-handed β-solenoid with a triangular cross-section that forms three protein surfaces, named A, B and C faces...
March 13, 2018: FEBS Journal
Yohei Katsuyama, Yukari Sato, Yoshinori Sugai, Yousuke Higashiyama, Miki Senda, Toshiya Senda, Yasuo Ohnishi
Enzymes belonging to the aspartase/fumarase superfamily catalyze elimination of various functional groups from succinate derivatives and play an important role in primary metabolism and aromatic compound degradation. Recently, an aspartase/fumarase superfamily enzyme, CreD, was discovered in cremeomycin biosynthesis. This enzyme catalyzes the elimination of nitrous acid from nitrosuccinate synthesized from aspartate by CreE, a flavin-dependent monooxygenase. Nitrous acid generated by this pathway is an important precursor of the diazo group of cremeomycin...
March 5, 2018: FEBS Journal
Neil Swainston, Antonio Baici, Barbara M Bakker, Athel Cornish-Bowden, Paul F Fitzpatrick, Peter Halling, Thomas S Leyh, Claire O'Donovan, Frank M Raushel, Udo Reschel, Johann M Rohwer, Santiago Schnell, Dietmar Schomburg, Keith F Tipton, Ming-Daw Tsai, Hans V Westerhoff, Ulrike Wittig, Roland Wohlgemuth, Carsten Kettner
No abstract text is available yet for this article.
March 2, 2018: FEBS Journal
Ebenezer Ajewole, Liliana Santamaria-Kisiel, Agnieszka Pajak, Mariusz Jaskolski, Frédéric Marsolais
L-asparaginases (EC play an important role in nitrogen mobilization in plants. Here, we investigated the biochemical and biophysical properties of potassium dependent (PvAspG1) and potassium independent (PvAspG-T2) L-asparaginases from Phaseolus vulgaris. Our previous studies revealed that PvAspG1 requires potassium for catalytic activation and its crystal structure suggested that Ser-118 in the activation loop plays a critical role in coordinating the metal cation. This amino acid residue is replaced by isoleucine in PvAspG-T2...
March 2, 2018: FEBS Journal
Selma Tuzlak, Manuel D Haschka, Anna-Maria Mokina, Thomas Rülicke, Suzanne Cory, Verena Labi, Andreas Villunger
Overexpression of BCLX and BFL1/A1 has been reported in various human malignancies and is associated with poor prognosis and drug-resistance, identifying these pro-survival BCL2 family members as putative drug-targets. We have generated transgenic mice that express human BFL1 or human BCLX protein throughout the hematopoietic system under the control of the Vav-gene promoter. Hematopoiesis is normal in both the Vav-BFL1 and Vav-BCLX transgenic (TG) mice and susceptibility to spontaneous hematopoietic malignancies is not increased...
March 2, 2018: FEBS Journal
Tyler D R Vance, Laurie A Graham, Peter L Davies
Out of the dozen different ice-binding protein (IBP) structures known, the DUF3494 domain is the most widespread, having been passed many times between prokaryotic and eukaryotic microorganisms by horizontal gene transfer. This ~25-kDa β-solenoid domain with an adjacent parallel α-helix is most commonly associated with an N-terminal secretory signal peptide. However, examples of the DUF3494 domain preceded by tandem Bacterial Immunoglobulin-like (BIg) domains are sometimes found, though uncharacterized. Here we present one such protein (SfIBP_1) from the Antarctic bacterium Shewanella frigidimarina...
March 2, 2018: FEBS Journal
Shu-Fang Hsu, Yu-Bin Lee, Ying-Chu Lee, Ai-Ling Chung, Maria Karmella Apaya, Lie-Fen Shyur, Ching-Feng Cheng, Feng-Ming Ho, Tzu-Ching Meng
Tumor necrosis factor (TNF)-α activates a diverse array of signaling pathways in vascular endothelial cells (ECs), leading to the inflammatory phenotype that contributes to the vascular dysfunction and neutrophil emigration in patients with sepsis. To date, it is not well understood what key regulator might coordinate signaling pathways to achieve inflammatory response in TNF-α-stimulated ECs. This study investigated the role of dual specificity phosphatase-6 (DUSP6) in the regulation of endothelial inflammation...
March 1, 2018: FEBS Journal
Rashmi Dahiya, Krishnamurthy Natarajan
TAF6, bearing histone H4-like histone fold domain, is a subunit of the core TAF module in TFIID and SAGA transcriptional regulatory complexes. We isolated and characterized several yeast TAF6 mutants bearing amino acid substitutions in the histone fold domain, the middle region or the HEAT repeat domain. The TAF6 mutants were highly defective for transcriptional activation by the Gcn4 and Gal4 activators. Chromatin immunoprecipitation assays showed that the TAF6-HFD and the TAF6-HEAT domain mutations independently abrogated the promoter occupancy of TFIID and SAGA complex in vivo...
February 27, 2018: FEBS Journal
F Berardinelli, A Sgura, A Facoetti, S Leone, B Vischioni, M Ciocca, A Antoccia
The pentacyclic acridine RHPS4 is a highly potent and specific G-quadruplex (G4) ligand, which binds and stabilizes telomeric G4 leading to the block of the replication forks at telomeres and consequently to telomere dysfunctionalization. In turn, the cell recognizes unprotected telomeres as DNA double-strand breaks with consequent activation of DNA repair response at telomeres, cellular growth impairment and death. Data from the literature showed the capability of this compound to sensitize U251MG glioblastoma radioresistant cell line to X-rays sparsely ionizing radiations...
February 27, 2018: FEBS Journal
Shubhangi Kaushik, Sérgio M Marques, Prashant Khirsariya, Kamil Paruch, Lenka Libichova, Jan Brezovsky, Zbynek Prokop, Radka Chaloupkova, Jiri Damborsky
The traditional way of rationally engineering enzymes to change their biocatalytic properties utilizes the modifications of their active sites. Another emerging approach is the engineering of structural features involved in the exchange of ligands between buried active sites and the surrounding solvent. However, surprisingly little is known about the effects of mutations that alter the access tunnels on the enzymes' catalytic properties, and how these tunnels should be redesigned to allow fast passage of cognate substrates and products...
February 25, 2018: FEBS Journal
Cristiane Cecatto, Alexandre Umpierrez Amaral, Janaína Camacho da Silva, Alessandro Wajner, Mariana de Oliveira Vargas Schimit, Lucas Henrique Rodrigues da Silva, Simone Magagnin Wajner, Ângela Zanatta, Roger Frigério Castilho, Moacir Wajner
We studied the effects of the major long-chain fatty acids accumulating in very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency, namely cis-5-tetradecenoic acid (Cis-5) and myristic acid (Myr), on important mitochondrial functions in isolated mitochondria from heart, cardiac fibers of juvenile rats and cardiomyocytes. Cis-5 and Myr at pathological concentrations markedly reduced mitochondrial membrane potential (ΔΨm), matrix NAD(P)H pool, Ca2+ retention capacity, ADP- (state 3) and CCCP-stimulated (uncoupled) respiration and ATP generation...
February 24, 2018: FEBS Journal
Gyles E Cozier, Sylva L Schwager, Rajni K Sharma, Kelly Chibale, Edward D Sturrock, K Ravi Acharya
Angiotensin-1 converting enzyme (ACE) is a zinc metallopeptidase that consists of two homologous catalytic domains (known as nACE and cACE) with different substrate specificities. Based on kinetic studies it was previously reported that sampatrilat, a tight-binding inhibitor of ACE, Ki =13.8 nM and 171.9 nM for cACE and nACE respectively [Sharma et al., Journal of Chemical Information and Modeling (2016), 56, 2486-2494] was 12.4-fold more selective for cACE. In addition, samAsp, in which an aspartate group replaces the sampatrilat lysine, was found to be a non-specific and lower micromolar affinity inhibitor...
February 24, 2018: FEBS Journal
Daniel Hughes, Giovanna R Mallucci
The unfolded protein response (UPR) is a highly conserved protein quality control mechanism, activated in response to Endoplasmic Reticulum (ER) stress. Signaling is mediated through three branches, PERK, IRE1 and ATF6, respectively, that together provide a coordinated response that contributes to overcoming disrupted proteostasis. PERK branch activation predominantly causes a rapid reduction in global rates of translation, whilst the IRE1 and ATF6 branch signaling induce a transcriptional response resulting in expression of chaperones and components of the protein degradation machinery...
February 24, 2018: FEBS Journal
Long Zhang, Zhi Lv, Jing Xu, Chenglong Chen, Qiaofeng Ge, Pengcui Li, Dinglu Wei, Zhuangzhuang Wu, Xiaojuan Sun
The vascular endothelial growth factor (VEGF) A and vascular endothelial growth factor receptor 1 (VEGFR1) signaling is crucial for angiogenesis and progression of osteosarcoma (OS). However, the regulation of the VEGF/VEGFR1 expression is still unclear in OS. Here, we show lower levels of microRNA-134 (miR-134) in OS tissues and cells. Induction of miR-134 over-expression significantly reduced the proliferation of Saos-2 cells and their secretion of pro-angiogenic factors, but increased the frequency of apoptotic Saos-2 cells...
February 23, 2018: FEBS Journal
Jennifer Susanne Esser, Rahel Elisabeth Steiner, Meike Deckler, Hannah Schmitt, Bianca Engert, Sandra Link, Anne Charlet, Cam Patterson, Christoph Bode, Qian Zhou, Martin Moser
The bone morphogenetic protein (BMP) signaling pathway plays a central role during vasculature development. Mutations or dysregulation of the BMP pathway members have been linked to arteriovenous malformations. In the present study, we investigated the effect of the BMP modulators BMPER and twisted gastrulation protein homolog 1 (TWSG1) on arteriovenous specification during zebrafish development and analyzed downstream Notch signaling pathway in human endothelial cells. Silencing of bmper and twsg1b in zebrafish embryos by morpholinos resulted in a pronounced enhancement of venous ephrinB4a marker expression and concomitant dysregulated arterial ephrinb2a marker expression detected by in situ hybridization...
February 23, 2018: FEBS Journal
Luiz Augusto Perandini, Patricia Chimin, Diego da Silva Lutkemeyer, Niels Olsen Saraiva Câmara
Chronic inflammation impairs skeletal muscle regeneration. Although many cells are involved in chronic inflammation, macrophages seem to play an important role in impaired muscle regeneration since these cells are associated with skeletal muscle stem cell (namely, satellite cells) activation and fibro-adipogenic progenitor cell (FAP) survival. Specifically, an imbalance of M1 and M2 macrophages seems to lead to impaired satellite cell activation, and these are the main cells that function during skeletal muscle regeneration, after muscle damage...
February 23, 2018: FEBS Journal
Patrycja Kaczara, Bartosz Proniewski, Christopher Lovejoy, Kamil Kuś, Roberto Motterlini, Andrey Y Abramov, Stefan Chlopicki
Carbon monoxide-releasing molecules (CO-RMs) induce nitric oxide (NO) release (which requires NADPH), and Ca2+ -dependent signalling; however, their contribution in mediating endothelial responses is not clear. Here, we studied the effects of CO liberated from CORM-401 on NO production, calcium signalling and pentose phosphate pathway (PPP) activity in human endothelial cell line (EA.hy926). CORM-401 induced NO production and two types of calcium signalling: a peak-like calcium signal and a gradual increase in cytosolic calcium...
February 21, 2018: FEBS Journal
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