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FEBS Journal

Maik Dahlhoff, Nadege Gaborit, Sebastian Bultmann, Heinrich Leonhardt, Yosef Yarden, Marlon R Schneider
While the epidermal growth factor receptor (EGFR) is an established regulator of skin development and homeostasis, the functions of the related tyrosine kinase receptors ERBB2 and ERBB3 in this tissue have only recently been examined. Previously reported, skin-specific deletion of each of these receptors in mice resulted in similar defects in keratinocyte proliferation and migration, resulting in impaired wound healing and tumorigenesis. Because both ERBB2 and ERBB3 are targets for treating an array of cancer types, it is important to examine the consequences of receptor inhibition in human keratinocytes...
August 14, 2017: FEBS Journal
Li Ou, Megan Matthews, Xiaodong Pang, Huan-Xiang Zhou
Intrinsically disordered proteins (IDPs) play key roles in signaling and regulation. Many IDPs undergo folding upon binding to their targets. We have proposed that coupled folding and binding of IDPs generally follow a dock-and-coalesce mechanism, whereby a segment of the IDP, through diffusion, docks to its cognate subsite and, subsequently, the remaining segments coalesce around their subsites. Here, by a combination of experiment and computation, we determined the precise form of dock-and-coalesce operating in the association between the intrinsically disordered GTPase binding domain (GBD) of the Wiskott-Aldrich Syndrome protein (WASP) and the Cdc42 GTPase...
August 14, 2017: FEBS Journal
Chan-Hee Kim, Ye Jin Lee, Hye-Jin Go, Hye Young Oh, Tae Kwan Lee, Ji Been Park, Nam Gyu Park
Recent studies suggest that vertebrate and invertebrate defensins have evolved from two independent ancestors, and that both defensins could share origins with animal toxins. Here, we purified novel sea anemone neurotoxin (BDS)-like antimicrobial peptides (AMPs)-Crassicorin-I and its putative homolog (Crassicorin-II)-from the pharynx extract of an anthozoan sea anemone (Urticina crassicornis). Based on structural analyses and cDNA cloning, mature Crassicorin-I represents a cationic AMP likely generated from a precursor and comprising 40 amino acid residues, including six cysteines forming three intramolecular disulphide bonds...
August 10, 2017: FEBS Journal
Keith Burridge
Focal adhesions are specialized sites within the cell where clustered integrin receptors interact with the extracellular matrix on the outside of cells and with the actin cytoskeleton on the inside. They provide strong adhesion to the matrix and transmit mechanical tension generated within cells across the plasma membrane to the external environment. Additionally, they act as scaffolds for many signaling pathways triggered by integrin engagement or mechanical force exerted on cells. Here I describe my personal perspective on focal adhesion research which I have witnessed since the initial discovery and description of focal adhesions as electron dense regions of the ventral plasma nearly half a century ago...
August 10, 2017: FEBS Journal
Juline Poirson, Elise Biquand, Marie-Laure Straub, Patricia Cassonnet, Yves Nominé, Louis Jones, Sylvie van der Werf, Gilles Travé, Katia Zanier, Yves Jacob, Caroline Demeret, Murielle Masson
Protein ubiquitination and its reverse reaction, deubiquitination, regulate protein stability, protein binding activity and their subcellular localization. These reactions are catalyzed by the enzymes E1, E2 and E3 Ubiquitin ligases and deubiquitinases. The ubiquitin-proteasome system is targeted by viruses for the sake of their replication and to escape host immune response. To identify novel partners of HPV16 E6 and E7 proteins, we assembled and screened a library of 590 cDNAs related to the UPS by using the Gaussia princeps luciferase Protein Complementation Assay...
August 8, 2017: FEBS Journal
Kelsey M Kean, Russell A Carpenter, Vittorio Pandini, Giuliana Zanetti, Andrea R Hall, Rick Faber, Alessandro Aliverti, P Andrew Karplus
Ferredoxin-NADP(+) reductase (FNR) is an FAD-containing enzyme best known for catalyzing the transfer of electrons from ferredoxin (Fd) to NADP(+) to make NADPH during photosynthesis. It is also the prototype for a broad enzyme superfamily, including the NADPH oxidases (NOXs) that all catalyze similar FAD-enabled electron transfers between NAD(P)H and one-electron carriers. Here we define further mechanistic details of the NAD(P)H This article is protected by copyright. All rights reserved. ⇌ FAD hydride-transfer step of the reaction based on spectroscopic studies and high resolution (~1...
August 7, 2017: FEBS Journal
Mengyang Li, Wei Ding, Teng Sun, Muhammad Akram Tariq, Tao Xu, Peifeng Li, Jianxun Wang
Circular RNAs (circRNAs) are a newly discovered type of RNAs generated by back-splicing of precursor mRNA (pre-mRNA) and found in many species. They are, expressed in a tissue-specific manner and fulfill regulatory activities in many biological processes. Recent research revealed that circRNAs play critical roles in the development and pathologies of the cardiovascular system. Some of these circRNAs showed aberrant expression and regulatory activities during heart disease including heart failure and cardiac infarction and hypertrophy...
August 7, 2017: FEBS Journal
Zélia Gouveia, Ana Rita Carlos, Xiaojing Yuan, Frederico Aires-da-Silva, Roland Stocker, Ghassan J Maghzal, Sónia S Leal, Cláudio M Gomes, Smilja Todorovic, Olga Iranzo, Susana Ramos, Ana Catarina Santos, Iqbal Hamza, João Gonçalves, Miguel P Soares
Extracellular hemoglobin (Hb), a byproduct of hemolysis, can release its prosthetic heme groups upon oxidation. This produces metabolically active heme that is exchangeable between acceptor proteins, macromolecules and low molecular weight ligands, termed here labile heme. As it accumulates in plasma labile heme acts in a pro-oxidant manner and regulates cellular metabolism while exerting pro-inflammatory and cytotoxic effects that foster the pathogenesis of hemolytic diseases. Here we developed and characterized a panel of heme-specific single domain antibodies (sdAbs) that together with a cellular-based heme reporter assay, allow for quantification and characterization of labile heme in plasma during hemolytic conditions...
August 7, 2017: FEBS Journal
Marta Szabat, Ryszard Kierzek
Nowadays, decades after the discovery of the right-handed B-DNA, it is well known that nucleic acids have a great conformational flexibility, exhibiting a large polymorphism of their structures. In nature, DNA and RNA exist in an antiparallel orientation, stabilized by Watson-Crick base pairs. However, in some cases, nucleic acid fragments with specific nucleotide sequences can adopt a parallel orientation involving noncanonical base pairing. Interestingly, parallel-stranded duplexes have been found in specific chromosome regions...
August 3, 2017: FEBS Journal
Yuanwu Ma, Lei Yu, Shuo Pan, Shan Gao, Wei Chen, Xu Zhang, Wei Dong, Jing Li, Rui Zhou, Lan Huang, Yunlin Han, Lin Bai, Li Zhang, Lianfeng Zhang
The rat is an important laboratory animal for physiological, toxicological and pharmacological studies. CRISPR/Cas9 is a simple and efficient tool to generate precise genetic modifications in rats, which will promote the accumulation of rat genetic resources and enable more precise studies of gene function. To monitor Cre/loxP-mediated excision in vivo, we generated a Cre reporter rat strain (Rosa26-imCherry) by knockin of a Cre reporter cassette at Rosa26 locus using CRISPR/Cas9. Rosa26-imCherry rats exhibited inducible expression of the mCherry cassette (imCherry) using the Cre/loxP system, whereas normal rats exhibited ubiquitous expression of eGFP but not mCherry in the whole body...
August 1, 2017: FEBS Journal
Christin Wallstab, Dimitra Eleftheriadou, Theresa Schulz, Georg Damm, Daniel Seehofer, Jürgen Borlak, Hermann-Georg Holzhütter, Nikolaus Berndt
The liver responds to elevated plasma concentrations of free fatty acids (FFAs) with an enhanced uptake of FFAs and their esterification to triacylglycerol (TAG). On the long term this may result in massive hepatic TAG accumulation called steatosis hepatitis. In hepatocytes, the poor water-soluble TAG is packed in specialized organelles: Lipid droplets (LDs) serving as transient cellular deposit and lipoproteins (LPs) transporting TAG and cholesterol esters to extra-hepatic tissues. The dynamics of these organelles is controlled by a variety of regulatory surface proteins (RSPs)...
August 1, 2017: FEBS Journal
Avital Sarusi Portuguez, Michal Schwartz, Rasmus Siersbaek, Ronni Nielsen, Myong-Hee Sung, Susanne Mandrup, Tommy Kaplan, Ofir Hakim
The three dimensional folding of mammalian genomes is cell-type specific and difficult to alter suggesting that it is an important component of gene regulation. However, given the multitude of chromatin associating factors, the mechanisms driving the co-localization of active chromosomal domains and the role of this organization in regulating the transcription program in adipocytes are not clear. Analysis of genome-wide chromosomal associations revealed cell type-specific spatial clustering of adipogenic genes in 3T3-L1 cells...
July 29, 2017: FEBS Journal
Aida Peña-Blanco, Ana J García-Sáez
Bax and Bak are members of the Bcl-2 family and core regulators of the intrinsic pathway of apoptosis. Upon apoptotic stimuli, they are activated and oligomerize at the mitochondria outer membrane to mediate its permeabilization, which is considered a key step in apoptosis. However, the molecular mechanism underlying Bax and Bak function has remained a key question in the field. Here we review recent structural and biophysical evidence that has changed our understanding of how Bax and Bak promote mitochondrial outer membrane permeabilization...
July 29, 2017: FEBS Journal
Alfonso Galan, Gloria Lozano, David Piñeiro, Encarnacion Martinez-Salas
RNA-protein interactions play a pivotal role in the function of picornavirus internal ribosome entry site (IRES) elements. Here we analysed the impact of Ras GTPase SH3 domain binding protein 1 (G3BP1) in the IRES activity of foot-and-mouth disease virus (FMDV). We found that G3BP1 interacts directly with three distinct sequences of the IRES element using RNA electrophoretic mobility-shift assays. Analysis of the interaction with domain 5 indicated that the G3BP1 binding-site is placed at the single-stranded region although it allows large sequence heterogeneity and the hairpin located upstream of this region enhances retarded complex formation...
July 29, 2017: FEBS Journal
Idir Malki, François-Xavier Cantrelle, Yoann Sottejeau, Guy Lippens, Jean-Charles Lambert, Isabelle Landrieu
Bridging integrator 1 bin1 gene is a genetic determinant of Alzheimer's disease and has been reported to modulate Alzheimer's pathogenesis through pathway(s) involving Tau. The functional impact of Tau/BIN1 interaction as well as the molecular details of this interaction are still not fully resolved. As a consequence, how BIN1 through its interaction with Tau affects Alzheimer's disease risk is also still not determined. To progress in this understanding, interaction of Tau with two BIN1 isoforms was investigated using Nuclear Magnetic Resonance spectroscopy...
July 29, 2017: FEBS Journal
Vladimir N Uversky, Nawal Abd El-Baky, Esmail M El-Fakharany, Amira Sabry, Ehab H Mattar, Alexey V Uversky, Elrashdy M Redwan
Tumor necrosis factor-α (TNF-α) is a pleiotropic inflammatory cytokine that exerts potent cytotoxic effects on solid tumor cells, while not affecting their normal counterparts. It is also known that TNF-α exerts many of its biological functions via interaction with specific receptors. To understand the potential roles of intrinsic disorder in the functioning of this important cytokine, we explored the peculiarities of intrinsic disorder distribution in human TNF-α and its homologues from various species, ranging from zebrafish to chimpanzee...
July 26, 2017: FEBS Journal
Marina Nawata, Hirotaka Tsutsumi, Yuta Kobayashi, Satoru Unzai, Shouhei Mine, Tsutomu Nakamura, Koichi Uegaki, Hironari Kamikubo, Mikio Kataoka, Daizo Hamada
Amyloid light chain (AL) amyloidosis is a protein-misfolding disease characterized by accumulation of immunoglobulin light chains (LCs) into amyloid fibrils. Dimerization of full length or variable domain (VL ) of LC serves to stabilize the native state and prevent the formation of amyloid fibrils. We here analyzed the thermodynamic properties of dimerization and unfolding reactions by nonamyloidogenic VL from REI LC or its monomeric Y96K mutant using sedimentation velocity and circular dichroism. The data indicate that the equilibrium shifts to native dimerization for wild type REI VL by elevating temperature due to the negative enthalpy change for dimer dissociation (-81...
July 24, 2017: FEBS Journal
Meng Zhang, Xiao-Wei Yu, Yan Xu, Paula Jouhten, Gurla V T Swapna, Ralf W Glaser, John F Hunt, Gaetano T Montelione, Hannu Maaheimo, Thomas Szyperski
Carbon metabolism of Crabtree-negative yeast Pichia pastoris was profiled using (13) C nuclear magnetic resonance (NMR) to delineate regulation during exponential growth and to study the import of two precursors for branched-chain amino acid biosynthesis, α-ketoisovalerate and α-ketobutyrate. Cells were grown in aerobic batch cultures containing (a) only glucose, (b) glucose along with the precursors, or (c) glucose and Val. The study provided the following new insights. First, (13) C flux ratio analyses of central metabolism reveal an unexpectedly high anaplerotic supply of the tricarboxylic acid cycle for a Crabtree-negative yeast, and show that a substantial fraction of glucose catabolism proceeds through the pentose phosphate pathway...
July 21, 2017: FEBS Journal
Qianlin Xiao, Yayun Wang, Jia Du, Hui Li, Bin Wei, Yongbin Wang, Yangping Li, Guowu Yu, Hanmei Liu, Junjie Zhang, Yinghong Liu, Yufeng Hu, Yubi Huang
The biosynthesis of starch is a complex process that depends on the regulatory mechanisms of different functional enzymes and transcriptional regulation plays an important role in this process. Brittle 1, encoded by BT1, is a transporter of adenosine diphosphate-glucose, which plays an important role in the biosynthesis of starch in the endosperm of cereals. Here, we report that the promoter (pZmBT1) of the maize BT1 homolog, ZmBT1, contains an MBSI site (TAACTG), which is important for its activity. Moreover, high expression level of the gene for ZmMYB14 transcription factor was observed in the maize endosperm; its expression pattern was similar to those of the starch synthesis related genes in maize seeds...
July 20, 2017: FEBS Journal
Egor Y Plotnikov, Tatiana A Pavlenko, Irina B Pevzner, Ljubava D Zorova, Vasily N Manskikh, Denis N Silachev, Gennady T Sukhikh, Dmitry B Zorov
Neonatal kidney injury is a frequent pathology, especially among premature infants. The search for effective nephroprotection requires the creation of adequate experimental models of nephropathy in newborns. In this study, we explored the development of acute kidney injury (AKI) in neonatal rats during hypoxia or administration of endotoxin. We found that 2-h hypoxia (8% O2 ) and the intraperitoneal injection of 4 mg/kg lipopolysaccharide (LPS) causes the appearance of AKI markers, such as КIM-1 and NGAL in the rat urine after 24 and 72 h of exposure...
July 17, 2017: FEBS Journal
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