The AQP2 mutation V71M causes nephrogenic diabetes insipidus in humans but does not impair the function of a bacterial homolog
Publication date: Available online 26 July 2015 Source:FEBS Open Bio Author(s): Noreen Klein, Nadine Kümmerer, Dominika Hobernik, Dirk Schneider Several point mutations have been identified in human aquaporins, but their effects on the function of the respective aquaporins are mostly enigmatic. We analyzed the impact of the aquaporin 2 mutation V71M, which causes nephrogenic diabetes insipidus in humans, on aquaporin structure and activity, using the bacterial aquaglyceroporin GlpF as a model. Importantly, the sequence and structure around the V71M mutation is highly conserved between aquaporin 2 and GlpF. The...
Source: FEBS Open Bio - July 26, 2015 Category: Molecular Biology Source Type: research
The synaptotagmin juxtamembrane domain is involved in neuroexocytosis
Publication date: 2015 Source:FEBS Open Bio, Volume 5 Author(s): Paola Caccin, Michele Scorzeto, Nunzio Damiano, Oriano Marin, Aram Megighian, Cesare Montecucco Synaptotagmin is a synaptic vesicle membrane protein which changes conformation upon Ca2+ binding and triggers the fast neuroexocytosis that takes place at synapses. We have synthesized a series of peptides corresponding to the sequence of the cytosolic juxtamembrane domain of synaptotagmin, which is highly conserved among different isoforms and animal species, with or without either a hexyl hydrophobic chain or the hexyl group plus a fluorescein mo...
Source: FEBS Open Bio - July 25, 2015 Category: Molecular Biology Source Type: research
Corrigendum to “Discovery of novel interacting partners of PSMD9, a proteasomal chaperone: Role of an Atypical and versatile PDZ-domain motif interaction and identification of putative functional modules” [FEBS Open Bio 4 (2014) 571–583]
Publication date: Available online 28 June 2015 Source:FEBS Open Bio Author(s): Nikhil Sangith, Kannan Srinivasaraghavan, Indrajit Sahu, Ankita Desai, Spandana Medipally, Arun Kumar Somavarappu, Chandra Verma, Prasanna Venkatraman (Source: FEBS Open Bio)
Source: FEBS Open Bio - July 17, 2015 Category: Molecular Biology Source Type: research
An HcpR paralog of Desulfovibrio gigas provides protection against nitrosative stress
Publication date: Available online 9 July 2015 Source:FEBS Open Bio Author(s): Sofia M. da Silva, Catarina Amaral, Susana S. Neves, Cátia Santos, Catarina Pimentel, Claudina Rodrigues-Pousada Desulfovibrio gigas belongs to the group of sulfate reducing bacteria (SRB). These ubiquitous and metabolically versatile microorganisms are often exposed to reactive nitrogen species (RNS). Nonetheless, the mechanisms and regulatory elements involved in nitrosative stress protection are still poorly understood. The transcription factor HcpR has emerged as a putative regulator of nitrosative stress response among ana...
Source: FEBS Open Bio - July 17, 2015 Category: Molecular Biology Source Type: research
Ubiquitin is a versatile scaffold protein for the generation of molecules with de novo binding and advantageous drug-like properties
Publication date: Available online 10 July 2015 Source:FEBS Open Bio Author(s): Florian Job, Florian Settele, Susan Lorey, Chris Rundfeldt, Lars Baumann, Annette G. Beck-Sickinger, Ulrich Haupts, Hauke Lilie, Eva Bosse-Doenecke In the search for effective therapeutic strategies, protein-based biologicals are under intense development. While monoclonal antibodies represent the majority of these drugs, other innovative approaches are exploring the use of scaffold proteins for the creation of binding molecules with tailor-made properties. Ubiquitin is especially suited for this strategy due to several ke...
Source: FEBS Open Bio - July 17, 2015 Category: Molecular Biology Source Type: research
Histone H3 Ser57 and Thr58 phosphorylation in the brain of 5XFAD mice
Publication date: Available online 25 June 2015 Source:FEBS Open Bio Author(s): Kyle W. Anderson , Natalia Mast , Irina A. Pikuleva , Illarion V. Turko Alzheimer’s disease has been shown to have a global reduction in gene expression, called an epigenetic blockade, which may be regulated by histone post-translational modifications. Histone H3 has been shown to be highly regulated by phosphorylation. We, therefore, chose H3 for investigation of phosphorylation of the core sites serine-57 (S57) and threonine-58 (T58). Hemispheres of brains from a mouse model of rapid amyloid deposition (5XFAD) were used for measurem...
Source: FEBS Open Bio - June 25, 2015 Category: Molecular Biology Source Type: research
2D DIGE proteomic analysis highlights delayed postnatal repression of α-fetoprotein expression in homocystinuria model mice
Publication date: Available online 22 June 2015 Source:FEBS Open Bio Author(s): Shotaro Kamata , Noriyuki Akahoshi , Isao Ishii Cystathionine β-synthase-deficient (Cbs –/–) mice, an animal model for homocystinuria, exhibit hepatic steatosis and juvenile semilethality via as yet unknown mechanisms. The plasma protein profile of Cbs –/– mice was investigated by proteomic analysis using two-dimensional difference gel electrophoresis and matrix-assisted laser desorption/ionization-time of flight/mass spectrometry. We found hyperaccumulation of α-fetoprotein (AFP) and downregulation of most other plasma protein...
Source: FEBS Open Bio - June 23, 2015 Category: Molecular Biology Source Type: research
Small molecules inhibiting the nuclear localization of YAP/TAZ for chemotherapeutics and chemosensitizers against breast cancers
Publication date: Available online 22 June 2015 Source:FEBS Open Bio Author(s): Yusuke Oku , Naoyuki Nishiya , Toshiya Shito , Reiichiro Yamamoto , Yasufumi Yamamoto , Chihiro Oyama , Yoshimasa Uehara YAP and TAZ oncoproteins confer malignancy and drug resistance to various cancer types. We screened for small molecules that inhibit the nuclear localization of YAP/TAZ. Dasatinib, statins and pazopanib inhibited the nuclear localization and target gene expression of YAP and TAZ. All three drugs induced phosphorylation of YAP and TAZ, and pazopanib induced proteasomal degradation of YAP/TAZ. The sensitivities to th...
Source: FEBS Open Bio - June 23, 2015 Category: Molecular Biology Source Type: research
Studying antibiotic–membrane interactions via X-ray diffraction and fluorescence microscopy
Publication date: Available online 15 June 2015 Source:FEBS Open Bio Author(s): Yi-Ting Sun , Ping-Yuan Huang , Cheng-Hao Lin , Kuan-Rong Lee , Ming-Tao Lee Antibiotic drug resistance is a serious issue for the treatment of bacterial infection. Understanding the resistance to antibiotics is a key issue for developing new drugs. We used penicillin and sulbactam as model antibiotics to study their interaction with model membranes. Cholesterol was used to target the membrane for comparison with the well-known insertion model. Lamellar X-ray diffraction (LXD) was used to determine membrane thickness using successive d...
Source: FEBS Open Bio - June 16, 2015 Category: Molecular Biology Source Type: research
Uncleavable Nup98–Nup96 is functional in the fission yeast Schizosaccharomyces pombe
Publication date: Available online 12 June 2015 Source:FEBS Open Bio Author(s): Haruhiko Asakawa , Chie Mori , Chizuru Ohtsuki , Masaaki Iwamoto , Yasushi Hiraoka , Tokuko Haraguchi Essential nucleoporins Nup98 and Nup96 are coded by a single open reading frame, and produced by autopeptidase cleavage. The autocleavage site of Nup98–Nup96 is highly conserved in a wide range of organisms. To understand the importance of autocleavage, we examined a mutant that produces the Nup98–Nup96 joint molecule as a sole protein product of the nup189 + gene in the fission yeast Schizosaccharomyces pombe. Cells expressing on...
Source: FEBS Open Bio - June 14, 2015 Category: Molecular Biology Source Type: research
Proteasome inhibitors prevent cell death and prolong survival of mice challenged by Shiga toxin
We report that Stx induced rapid reduction of short-lived anti-apoptotic proteins followed by activation of caspase 9 and the progression of apoptosis. Proteasome inhibitors prevented the reduction of anti-apoptotic proteins, and inhibited caspase activation and apoptosis, suggesting that the reduction of anti-apoptotic proteins is a prerequisite for Stx-induced apoptosis. A clinically approved proteasome inhibitor, bortezomib, prolonged the survival of mice challenged by Stx. These results imply that proteasome inhibition may be a novel approach to prevent the fatal effects of Stx. (Source: FEBS Open Bio)
Source: FEBS Open Bio - June 13, 2015 Category: Molecular Biology Source Type: research
Epigallocatechin gallate (EGCG) suppresses lipopolysaccharide-induced inflammatory bone resorption, and protects against alveolar bone loss in mice
Publication date: Available online 12 June 2015 Source:FEBS Open Bio Author(s): Tsukasa Tominari , Chiho Matsumoto , Kenta Watanabe , Michiko Hirata , Florian M.W. Grundler , Chisato Miyaura , Masaki Inada Epigallocatechin gallate (EGCG), a major polyphenol in green tea, possesses antioxidant properties and regulates various cell functions. Here, we examined the function of EGCG in inflammatory bone resorption. In calvarial organ cultures, lipopolysaccharide (LPS)-induced bone resorption was clearly suppressed by EGCG. In osteoblasts, EGCG suppressed the LPS-induced expression of COX-2 and mPGES-1 mRNAs, as well...
Source: FEBS Open Bio - June 13, 2015 Category: Molecular Biology Source Type: research
Uncleavable Nup98-Nup96 is functional in the fission yeast Schizosaccharomyces pombe
Publication date: Available online 12 June 2015 Source:FEBS Open Bio Author(s): Haruhiko Asakawa , Chie Mori , Chizuru Ohtsuki , Masaaki Iwamoto , Yasushi Hiraoka , Tokuko Haraguchi Essential nucleoporins Nup98 and Nup96 are coded by a single open reading frame, and produced by autopeptidase cleavage. The autocleavage site of Nup98–Nup96 is highly conserved in a wide range of organisms. To understand the importance of autocleavage, we examined a mutant that produces the Nup98–Nup96 joint molecule as a sole protein product of the nup189 + gene in the fission yeast Schizosaccharomyces pombe. Cells expressing on...
Source: FEBS Open Bio - June 13, 2015 Category: Molecular Biology Source Type: research
Stepwise error-prone PCR and DNA shuffling changed the pH activity range and product specificity of the cyclodextrin glucanotransferase from an alkaliphilic Bacillus sp
Publication date: Available online 11 June 2015 Source:FEBS Open Bio Author(s): Susanne Melzer , Christian Sonnendecker , Christina Föllner , Wolfgang Zimmermann Cyclodextrin glucanotransferase (EC 2.4.1.19) from the alkaliphilic Bacillus sp. G-825-6 converts starch mainly to γ-cyclodextrin (CD8). A combination of error-prone PCR and DNA shuffling was used to obtain variants of this enzyme with higher product specificity for CD8 and a broad pH activity range. The variant S54 with seven amino acid substitutions showed a 1.2 fold increase in CD8-synthesizing activity and the product ratio of CD7:CD8 was shifted to ...
Source: FEBS Open Bio - June 12, 2015 Category: Molecular Biology Source Type: research
Reactive oxygen species induce Cox-2 expression via TAK1 activation in synovial fibroblast cells
Publication date: Available online 6 June 2015 Source:FEBS Open Bio Author(s): Yuta Onodera , Takeshi Teramura , Toshiyuki Takehara , Kanae Shigi , Kanji Fukuda Oxidative stress within the arthritis joint has been indicated to be involved in generating mediators for tissue degeneration and inflammation. COX-2 is a mediator in inflammatory action, pain and some catabolic reactions in inflamed tissues. Here, we demonstrated a direct relationship between oxidative stress and Cox-2 expression in the bovine synovial fibroblasts. Furthermore, we elucidated a novel mechanism, in which oxidative stress induced phosphoryla...
Source: FEBS Open Bio - June 7, 2015 Category: Molecular Biology Source Type: research
