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FEBS Letters

Pinreddy Karunakar, Ameek Bhalla, Abhay Sharma
Intergenerational inheritance of transcriptional responses induced by low temperature rearing has recently been shown in Drosophila. Besides germline inheritance, faecal transfer experiments indirectly suggested that the acquired microbiome may also have contributed to the transcriptional responses in offspring. Here, we analyze expression data on inheritance of the cold-induced effects in conjunction with previously reported transcriptomic differences between flies with a microbiota or axenic flies and provide support for a contribution of the acquired microbiome to the offspring phenotype...
February 19, 2019: FEBS Letters
Renate L M Jansen, Ida J van der Klei
The peroxisomal membrane protein Pex3 and its cytosolic interaction partner Pex19 have been implicated in peroxisomal membrane biogenesis. Although these peroxins have been extensively studied, no consensus has been reached yet on how they operate. Here, we discuss two major models of their function, namely, in direct insertion of proteins into the peroxisomal membrane or in formation of peroxisomal membrane protein-containing vesicles from the endoplasmic reticulum. Pex3 can also recruit other proteins to the peroxisomal membrane (e...
February 18, 2019: FEBS Letters
Iniyan Ganesan, Steven M Theg
Protein import into chloroplasts is carried out by the protein translocons at the outer and inner envelope membranes (TOC and TIC). Detailed structures for these translocons are lacking, with only a low-resolution TOC complex structure available. Recently, we showed that the TOC/TIC translocons can import folded proteins, a rather unique feat for a coupled double membrane system. We also determined the maximum functional TOC/TIC pore size to be 30-35 Å. Here, we discuss how such large pores could form and compare the structural dynamics of the pore-forming Toc75 subunit to its bacterial/mitochondrial Omp85 family homologs...
February 18, 2019: FEBS Letters
Tianlu Mo, Hong Yuan, Fangting Wang, Suze Ma, Jinxiu Wang, Ting Li, Guangfeng Liu, Shaoning Yu, Xiangshi Tan, Wei Ding, Qi Zhang
S-[(Z)-2-aminovinyl]-D-cysteine (AviCys) is a unique motif found in several classes of ribosomally synthesized and post-translationally modified peptides (RiPPs). Biosynthesis of AviCys requires flavin-dependent Cys decarboxylases, which are highly divergent among different RiPP classes. In this study, we solved the crystal structure of the cypemycin decarboxylase CypD. We show that CypD is structurally highly similar to lanthipeptide decarboxylases (LanDs) despite the absence of sequence similarities between them...
February 16, 2019: FEBS Letters
Hanane Hadj-Moussa, Alexander J Watts, Kenneth B Storey
A degree of regulation continues into death according to post-mortem transcriptome studies, which have identified "zombie genes" that come alive hours and days after organismal death. We hypothesized that hibernation, representing the closest natural mammalian phenomenon to death, would display similar gene expression profiles. Exploring zombie genes using qPCR and available transcriptomic resources from multiple torpid tissues in thirteen-lined ground squirrels show little in common with gene profiles observed following death...
February 15, 2019: FEBS Letters
Chung-Che Tsai, Fang-Ting Kuo, Sung-Bau Lee, Yu-Ting Chang, Hua-Wen Fu
Src plays a critical role in regulating cellular responses induced by protease-activated receptor 1 (PAR1). Here, we found that PAR1 activation induces lysosomal degradation of Src. Src is associated and trafficked together with activated PAR1 to early endosomes and then sorted to lysosomes for degradation. Blocking agonist-induced endocytosis of PAR1 by inhibition of dynamin activity suppresses PAR1-induced degradation of Src. However, Src activity is not required for agonist-induced PAR1 internalization; nor is it required for Src degradation upon PAR1 activation...
February 13, 2019: FEBS Letters
Matthias S Leisegang, Lunda Gu, Jens Preussner, Stefan Günther, Juliane Hitzel, Corina Ratiu, Andreas Weigert, Wei Chen, Eva C Schwarz, Mario Looso, Christian Fork, Ralf P Brandes
Histone3-Lysine9 (H3K9) residues not only control gene expression, but also contribute to RNA splicing. Here, the H3K9 histone demethylase PHF8 was investigated in endothelial cells for its involvement in alternative splicing. An angiogenic sprouting assay shows the importance of PHF8 for endothelial cells. Immunoprecipitation reveals that PHF8 interacts with U1 spliceosomal proteins, such as SRPK1 and snRNP70. We identify the histocompatibility antigen HLA-G as a target of PHF8. The inclusion of HLA-G intron-4, with concomitant RNA Polymerase II accumulation at this intron, is controlled by PHF8 and H3K9...
February 13, 2019: FEBS Letters
Ikhlaus Ahmed, Eric M Jones
Amyloid formation occurs via numerous complex mechanisms, often involving intermediates. This study examines the mechanism of amyloidogenesis in two N-terminal fragments of serum amyloid A (SAA), which are known to exhibit dramatically different amyloid structures. Fibrillization kinetics by these peptides are found to exhibit two unusual features: slower rates at higher peptide concentration, and complete insensitivity to addition of pre-formed seed. Additionally, we find that these peptides form micelle-like oligomers in solution...
February 13, 2019: FEBS Letters
Qingxin Li, Hui Qi Ng, CongBao Kang
Syndecans are single-span membrane proteins playing important roles in cell-cell and cell-matrix interactions. The transmembrane domain of syndecans is critical for signal transduction across the cell membrane. Here, the structure of the transmembrane domain of syndecan-2 in detergent micelles was investigated using solution NMR spectroscopy. Backbone resonance assignment was obtained, and NMR studies show that the transmembrane domain forms a helix in detergent micelles, which is also supported by the hydrogen and deuterium exchange experiment...
February 11, 2019: FEBS Letters
Artem P Gureev, Ekaterina A Shaforostova, Vasily N Popov, Anatoly A Starkov
Methylene blue (MB) is a promising prodrug to treat mitochondrial dysfunctions that is currently being used in clinical trials for Alzheimer's disease. MB can penetrate the blood brain barrier, accumulating in brain mitochondria where it acts as a redox mediator in the electron transfer chain (ETC). Mitochondrial flavins are thought to reduce MB, which is then oxidized by cytochrome c, thereby bypassing inhibited Complex I of ETC. We found that in mouse brain mitochondria, MB fails to restore the membrane potential and respiration inhibited by antimycin...
February 7, 2019: FEBS Letters
Bastian Vögeli, Seigo Shima, Tobias Erb, Tristan Wagner
3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) catalyses the last step in mevalonate biosynthesis. HMGR is the target of statin inhibitors that regulate cholesterol concentration in human blood. Here, we report the properties and structures of HMGR from the archaeon Methanothermococcus thermolithotrophicus (mHMGR). The structures of the apoenzyme and the NADPH-complex are highly similar to those of human HMGR. A notable exception is C-terminal helix (Lα10-11) that is straight in both mHMGR structures. This helix is kinked and closes the active site in the human enzyme ternary complex, pointing to a substrate-induced structural rearrangement of C-terminal in class-I HMGRs during the catalytic cycle...
January 31, 2019: FEBS Letters
Kiel Hards, Salome Molano Rodriguez, Charlotte Cairns, Gregory M Cook
There is a paucity of information on the unique components that pathogens use to form respiratory chains. It is not known why mycobacteria encode multiple succinate dehydrogenases (SDHs) to perform menaquinone-linked succinate oxidation, a thermodynamically unfavorable reaction (ΔG° = +21 kJ/mol). In other bacteria, specific di-heme SDHs overcome this using the proton-motive force. It is unknown if this holds true in mycobacteria. Here, succinate dehydrogenase 1 (Sdh1) from Mycobacterium smegmatis was purified and found to not contain heme-cofactors...
January 24, 2019: FEBS Letters
Jing Yuan How, Sofia Caria, Patrick O Humbert, Marc Kvansakul
Scribble (SCRIB) is an important adaptor protein that controls the establishment and maintenance of apico-basal cell polarity. To better understand how SCRIB controls cell polarity signalling via its PDZ domains, we investigated human SCRIB interactions with APC (adenomatous polyposis coli). We show that SCRIB PDZ1, PDZ2 and PDZ3 are the major interactors with the APC PDZ-binding motif (PBM), whereas SCRIB PDZ4 does not show detectable binding to APC. We then determined the crystal structure of SCRIB PDZ1 domain bound to the APC PBM...
January 19, 2019: FEBS Letters
Yuki Murayama, Naoya Yahagi, Yoshinori Takeuchi, Yuichi Aita, Zahra Mehrazad Saber, Nobuhiro Wada, EnXu Li, Xianying Piao, Yoshikazu Sawada, Akito Shikama, Yukari Masuda, Makiko Nishi-Tatsumi, Midori Kubota, Yoshihiko Izumida, Takafumi Miyamoto, Motohiro Sekiya, Takashi Matsuzaka, Yoshimi Nakagawa, Yoko Sugano, Hitoshi Iwasaki, Kazuto Kobayashi, Shigeru Yatoh, Hiroaki Suzuki, Hiroaki Yagyu, Yasushi Kawakami, Hitoshi Shimano
Glucocorticoids have various medical uses but are accompanied by side effects. The glucocorticoid receptor (GR) has been reported to regulate the clock genes, but the underlying mechanisms are incompletely understood. In the current study, we focused on the suppressive effect of the GR on the expression of Rev-erbα (Nr1d1), an important component of the clock regulatory circuits. Here we show that the GR suppresses Rev-erbα expression via the formation of a complex with CLOCK and BMAL1, which binds to the E-boxes in the Nr1d1 promoter...
January 19, 2019: FEBS Letters
Nisha Kriplani, Rory R Duncan, Nicholas R Leslie
Rearrangements of the actin cytoskeleton are regulated in part by dynamic localised activation and inactivation of Rho family small GTPases. SWAP70 binds to and activates the small GTPase RAC1 as well as binding to filamentous actin and PIP3 . We have developed an encoded biosensor, which uses Forster Resonance Energy Transfer (FRET) to reveal conformational changes in SWAP70 in live cells. SWAP70 adopts a distinct conformation at the plasma membrane, which in migrating glioma cells is enriched at the leading edge but does not always associate with its PIP3 -dependent translocation to the membrane...
January 12, 2019: FEBS Letters
Tingting Song, Haifeng Su, Wei Yin, Liming Wang, Rui Huang
LC3 is a key autophagy-related protein involved in both autophagosome formation and autophagy cargo recruitment. Despite these functions being exerted by deacetylated LC3, this protein is more abundantly distributed in its acetylated form. Here, we reveal that the stability and cargo recognition ability of LC3 are highly dependent on its acetylation. Through detecting the diffusion rate of soluble LC3 by fluorescence recovery after photobleaching (FRAP), we found that nutrient-state-related acetylation inhibited LC3 complex formation...
January 11, 2019: FEBS Letters
Natsuko F Inagaki, Fuyuki F Inagaki, Norihiro Kokudo, Atsushi Miyajima
Mesothelial cells, which cover the surface of visceral organs and serous cavities in mammals, play a crucial role in preventing adhesion. We previously reported that primary mesothelial progenitor cells (MPCs) can not only prevent postoperative adhesion but also promote liver regeneration after hepatectomy. Induced pluripotent stem cells (iPSCs) have the potential to be used for regenerative medicine. Here we have established a differentiation protocol for mouse iPSC-derived MPCs (miMPCs) via the exposure to defined factors, as well as purification using MPC-specific cell surface antigens...
January 4, 2019: FEBS Letters
Vinithra Iyer, Sivarajan T Chettiar, Manish Grover, Purusharth Rajyaguru, Rishi Kumar Nageshan, Utpal Tatu
We have previously shown that the Heat Shock Protein 90 (Hsp90) gene in G. lamblia is expressed from two ORFs localized 777 kb apart. The pre-mRNAs transcribed from these ORFs are stitched by a trans-splicing mechanism. Here we provide mechanistic details of this process by reconstituting the reaction using in vitro synthesized pre-mRNA substrates. Using RT-PCR, northern blot and nanostring technology we demonstrate that the in vitro synthesized pre-mRNAs have the capability to self-splice in the absence of nuclear proteins...
January 3, 2019: FEBS Letters
Siwen Ouyang, Tingting Liu, Xisheng Liu, Fu-Xiang Zhu, Fangming Zhu, Xueni Liu, Zhihai Peng
Recent studies have demonstrated that ubiquitin-specific protease 10 (USP10) plays a catalytic role in tumour suppression mainly by deubiquitinating its target proteins to enhance their stabilities. However, we found that USP10 could interact with and regulate the expression of oncogenic factor Musashi-2 (MSI2). We investigated whether USP10 positively regulates the expression of MSI2 by deubiquitination and confirmed the type of polyubiquitin chain that is linked to MSI2. We also explored the role of USP10 in regulating the proliferation of colon cancer through different experiments...
January 3, 2019: FEBS Letters
Chenghui Lu, Xue Zheng, Wei Zhang, Hongxin Zhao, Christopher A MacRaild, Raymond S Norton, Yonglong Zhuang, Junfeng Wang, Xuecheng Zhang
Merozoite surface protein 2 (MSP2) is a potential vaccine candidate against malaria, although its functional role is yet to be elucidated. Previous studies showed that MSP2 can interact with membranes, which may facilitate merozoite invasion into the host cell. The N-terminal 25 residues of MSP2 (MSP21-25 ), which may be aggregated on the merozoite surface, play a key role in the interaction with membranes. Here, we investigated the effects of MSP21-25 -membrane interactions on the conformation and aggregation of MSP21-25 and on membrane integrity, using nanodiscs and small unilamellar vesicles as mimetics of cell membranes...
December 26, 2018: FEBS Letters
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