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Study of two glycosyltransferases related to polysaccharide biosynthesis in Rhodococcus jostii RHA1 Biol. Chem. (IF 3.7) Pub Date : 2024-03-15 Antonela Estefania Cereijo, María Victoria Ferretti, Alberto Alvaro Iglesias, Héctor Manuel Álvarez, Matías Damian Asencion Diez
The bacterial genus Rhodococcus comprises organisms performing oleaginous behaviors under certain growth conditions and ratios of carbon and nitrogen availability. Rhodococci are outstanding producers of biofuel precursors, where lipid and glycogen metabolisms are closely related. Thus, a better understanding of rhodococcal carbon partitioning requires identifying catalytic steps redirecting sugar
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Apolipoprotein E-containing lipoproteins and their extracellular interactions with LRP1 affect LPS-induced inflammation Biol. Chem. (IF 3.7) Pub Date : 2024-03-15 Shogo Akahane, Hiroto Matsuura, Takahiro Kaido, Yoko Usami, Nau Ishimine, Takeshi Uehara, Kazuyoshi Yamauchi
The linkage between low-density lipoprotein receptor-related protein (LRP)1-mediated metabolism of apolipoprotein (apo) E-containing lipoproteins (apoE-LP) and the lipopolysaccharide (LPS)-induced inflammatory response contributes to the pathogenesis of sepsis; however, the underlying mechanisms are unclear. Therefore, in this study, the effects of apoE-LP and their constituents on the mRNA expression
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Yeast Bxi1/Ybh3 mediates conserved mitophagy and apoptosis in yeast and mammalian cells: convergence in Bcl-2 family Biol. Chem. (IF 3.7) Pub Date : 2024-03-11 Yuying Wang, Zhiyuan Hu, Maojun Jiang, Yanxin Zhang, Linjie Yuan, Ziqian Wang, Ting Song, Zhichao Zhang
The process of degrading unwanted or damaged mitochondria by autophagy, called mitophagy, is essential for mitochondrial quality control together with mitochondrial apoptosis. In mammalian cells, pan-Bcl-2 family members including conical Bcl-2 members and non-conical ones are involved in and govern the two processes. We have illustrated recently the BH3 receptor Hsp70 interacts with Bim to mediate
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Inhibition of Chk1 stimulates cytotoxic action of platinum-based drugs and TRAIL combination in human prostate cancer cells Biol. Chem. (IF 3.7) Pub Date : 2024-03-07 Martin Krkoška, Kamil Paruch, Tereza Šošolíková, Gerardo Vázquez-Gómez, Jarmila Herůdková, Jan Novotný, Petra Ovesná, Petr Sova, Alena Hyršlová Vaculová
Checkpoint kinase 1 (Chk1) plays an important role in regulation of the cell cycle, DNA damage response and cell death, and represents an attractive target in anticancer therapy. Small-molecule inhibitors of Chk1 have been intensively investigated either as single agents or in combination with various chemotherapeutic drugs and they can enhance the chemosensitivity of numerous tumor types. Here we
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KCTD5 regulates Ikaros degradation induced by chemotherapeutic drug etoposide in hematological cells Biol. Chem. (IF 3.7) Pub Date : 2024-02-29 Lan Ma, Changqing Yin, Yi Zhang, Jie Li, Liuzhi Shi, Tong Zhou, Xixi Huang, Yaqi Liu, Jiawei Cao, Guang Wu, Haihua Gu, Licai He
Therapy-related leukemia carries a poor prognosis, and leukemia after chemotherapy is a growing risk in clinic, whose mechanism is still not well understood. Ikaros transcription factor is an important regulator in hematopoietic cells development and differentiation. In the absence of Ikaros, lymphoid cell differentiation is blocked at an extremely early stage, and myeloid cell differentiation is also
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Cathepsin X deficiency alters the processing and localisation of cathepsin L and impairs cleavage of a nuclear cathepsin L substrate Biol. Chem. (IF 3.7) Pub Date : 2024-02-27 Bangyan Xu, Bethany M. Anderson, Simon J. Mountford, Philip E. Thompson, Justine D. Mintern, Laura E. Edgington-Mitchell
Proteases function within sophisticated networks. Altering the activity of one protease can have sweeping effects on other proteases, leading to changes in their activity, structure, specificity, localisation, stability, and expression. Using a suite of chemical tools, we investigated the impact of cathepsin X, a lysosomal cysteine protease, on the activity and expression of other cysteine proteases
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Biochemical evidence for conformational variants in the anti-viral and pro-metastatic protein IFITM1 Biol. Chem. (IF 3.7) Pub Date : 2024-02-21 Marta Nekulová, Marta Wyszkowska, Nela Friedlová, Lukáš Uhrík, Filip Zavadil Kokáš, Václav Hrabal, Lenka Hernychová, Bořivoj Vojtěšek, Ted R. Hupp, Michał R. Szymański
Interferon induced transmembrane proteins (IFITMs) play a dual role in the restriction of RNA viruses and in cancer progression, yet the mechanism of their action remains unknown. Currently, there is no data about the basic biochemical features or biophysical properties of the IFITM1 protein. In this work, we report on description and biochemical characterization of three conformational variants/oligomeric
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Bovine ultralong CDR-H3 derived knob paratopes elicit potent TNF-α neutralization and enable the generation of novel adalimumab-based antibody architectures with augmented features Biol. Chem. (IF 3.7) Pub Date : 2024-02-19 Paul Arras, Jasmin Zimmermann, Britta Lipinski, Bernhard Valldorf, Andreas Evers, Desislava Elter, Simon Krah, Achim Doerner, Enrico Guarnera, Vanessa Siegmund, Harald Kolmar, Lukas Pekar, Stefan Zielonka
In this work we have generated cattle-derived chimeric ultralong CDR-H3 antibodies targeting tumor necrosis factor α (TNF-α) via immunization and yeast surface display. We identified one particular ultralong CDR-H3 paratope that potently neutralized TNF-α. Interestingly, grafting of the knob architecture onto a peripheral loop of the CH3 domain of the Fc part of an IgG1 resulted in the generation of
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In-depth analysis of Gαs protein activity by probing different fluorescently labeled guanine nucleotides Biol. Chem. (IF 3.7) Pub Date : 2024-02-14 Anna Pepanian, Paul Sommerfeld, Furkan Ayberk Binbay, Dietmar Fischer, Markus Pietsch, Diana Imhof
G proteins are interacting partners of G protein-coupled receptors (GPCRs) in eukaryotic cells. Upon G protein activation, the ability of the Gα subunit to exchange GDP for GTP determines the intracellular signal transduction. Although various studies have successfully shown that both Gαs and Gαi have an opposite effect on the intracellular cAMP production, with the latter being commonly described
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Better safe than sorry: dual targeting antibodies for cancer immunotherapy Biol. Chem. (IF 3.7) Pub Date : 2024-01-31 Katrin Schoenfeld, Julia Harwardt, Harald Kolmar
Antibody-based therapies are revolutionizing cancer treatment and experience a steady increase from preclinical and clinical pipelines to market share. While the clinical success of monoclonal antibodies is frequently limited by low response rates, treatment resistance and various other factors, multispecific antibodies open up new prospects by addressing tumor complexity as well as immune response
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TIF1γ and SMAD4 regulation in colorectal cancer: impact on cell proliferation and liver metastasis Biol. Chem. (IF 3.7) Pub Date : 2024-01-23 Yanhui Wu, Bin Yu, Xi Ai, Wei Zhang, Weixun Chen, Arian Laurence, Mingzhi Zhang, Qian Chen, Yajie Shao, Bixiang Zhang
We investigated the effects of transcriptional intermediary factor 1γ (TIF1γ) and SMAD4 on the proliferation and liver metastasis of colorectal cancer (CRC) cells through knockdown of TIF1γ and/or SMAD4 and knockdown of TIF1γ and/or restoration of SMAD4 expression. Furthermore, we examined TIF1γ and SMAD4 expression in human primary CRC and corresponding liver metastatic CRC specimens. TIF1γ promoted
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Celastrol inhibits angiogenesis and the biological processes of MDA-MB-231 cells via the DEGS1/S1P signaling pathway Biol. Chem. (IF 3.7) Pub Date : 2023-12-11 Lulu Jia, Shengnan Zhu, Mingfei Zhu, Rongrong Nie, Lingyue Huang, Siyuan Xu, Yuqin Luo, Huazhen Su, Shaoyuan Huang, Qinyou Tan
Celastrol (Cel) shows potent antitumor activity in various experimental models. This study examined the relationship between Cel’s antivascular and antitumor effects and sphingolipids. CCK-8 assay, transwell assay, Matrigel, PCR-array/RT-PCR/western blotting/immunohistochemistry assay, ELISA and HE staining were used to detect cell proliferation, migration and invasion, adhesion and angiogenesis, mRNA
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Highlight: Horizons in Neuroscience - Organoids, Optogenetics and Remote Control. Biol. Chem. (IF 3.7) Pub Date : 2023-11-27 Rolf Heumann
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Visualization of the membrane surface and cytoskeleton of oligodendrocyte progenitor cell growth cones using a combination of scanning ion conductance and four times expansion microscopy Biol. Chem. (IF 3.7) Pub Date : 2023-11-11 Annika Haak, Heiko M. Lesslich, Irmgard D. Dietzel
Growth cones of oligodendrocyte progenitor cells (OPCs) are challenging to investigate with conventional light microscopy due to their small size. Especially substructures such as filopodia, lamellipodia and their underlying cytoskeleton are difficult to resolve with diffraction limited microscopy. Light microscopy techniques, which surpass the diffraction limit such as stimulated emission depletion
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Methionine restriction attenuates the migration and invasion of gastric cancer cells by inhibiting nuclear p65 translocation through TRIM47 Biol. Chem. (IF 3.7) Pub Date : 2023-11-09 Lin Xin, Yi-Wu Yuan, Chen-Xi Liu, Jie Sheng, Qi Zhou, Zhi-Yang Liu, Zhen-Qi Yue, Fei Zeng
The prevention and treatment of gastric cancer has been the focus and difficulty of medical research. We aimed to explore the mechanism of inhibiting migration and invasion of gastric cancer cells by methionine restriction (MR). The human gastric cancer cell lines AGS and MKN45 cultured with complete medium (CM) or medium without methionine were used for in vitro experiments. MKN45 cells were injected
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Heterogenous nuclear ribonucleoprotein D-like controls endothelial cell functions Biol. Chem. (IF 3.7) Pub Date : 2023-11-09 Sandra Fischer, Chiara Lichtenthaeler, Anastasiya Stepanenko, Florian Heyl, Daniel Maticzka, Katrin Kemmerer, Melina Klostermann, Rolf Backofen, Kathi Zarnack, Julia E. Weigand
HnRNPs are ubiquitously expressed RNA-binding proteins, tightly controlling posttranscriptional gene regulation. Consequently, hnRNP networks are essential for cellular homeostasis and their dysregulation is associated with cancer and other diseases. However, the physiological function of hnRNPs in non-cancerous cell systems are poorly understood. We analyzed the importance of HNRNPDL in endothelial
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Platelet-derived growth factor-stimulated pulmonary artery smooth muscle cells regulate pulmonary artery endothelial cell dysfunction through extracellular vesicle miR-409-5p Biol. Chem. (IF 3.7) Pub Date : 2023-10-31 Jeongyeon Heo, Hara Kang
Platelet-derived growth factor (PDGF)-induced changes in vascular smooth muscle cells (VSMCs) stimulate vascular remodeling, resulting in vascular diseases such as pulmonary arterial hypertension. VSMCs communicate with endothelial cells through extracellular vesicles (EVs) carrying cargos, including microRNAs. To understand the molecular mechanisms through which PDGF-stimulated pulmonary artery smooth
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Cathepsin L-mediated EGFR cleavage affects intracellular signalling pathways in cancer Biol. Chem. (IF 3.7) Pub Date : 2023-10-27 Marija Grozdanić, Barbara Sobotič, Monika Biasizzo, Tilen Sever, Robert Vidmar, Matej Vizovišek, Boris Turk, Marko Fonović
Proteolytic activity in the tumour microenvironment is an important factor in cancer development since it can also affect intracellular signalling pathways via positive feedback loops that result in either increased tumour growth or resistance to anticancer mechanisms. In this study, we demonstrated extracellular cathepsin L-mediated cleavage of epidermal growth factor receptor (EGFR) and identified
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Features of yeast RNA polymerase I with special consideration of the lobe binding subunits Biol. Chem. (IF 3.7) Pub Date : 2023-10-12 Katrin Schwank, Catharina Schmid, Tobias Fremter, Christoph Engel, Philipp Milkereit, Joachim Griesenbeck, Herbert Tschochner
Ribosomal RNAs (rRNAs) are structural components of ribosomes and represent the most abundant cellular RNA fraction. In the yeast Saccharomyces cerevisiae, they account for more than 60 % of the RNA content in a growing cell. The major amount of rRNA is synthesized by RNA polymerase I (Pol I). This enzyme transcribes exclusively the rRNA gene which is tandemly repeated in about 150 copies on chromosome
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Towards correlative archaeology of the human mind Biol. Chem. (IF 3.7) Pub Date : 2023-10-11 Lukasz Piszczek, Joanna Kaczanowska, Wulf Haubensak
Retracing human cognitive origins started out at the systems level with the top-down interpretation of archaeological records spanning from man-made artifacts to endocasts of ancient skulls. With emerging evolutionary genetics and organoid technologies, it is now possible to deconstruct evolutionary processes on a molecular/cellular level from the bottom-up by functionally testing archaic alleles in
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The good or the bad: an overview of autoantibodies in traumatic spinal cord injury Biol. Chem. (IF 3.7) Pub Date : 2023-10-03 Annika Guntermann, Katrin Marcus, Caroline May
Infections remain the most common cause of death after traumatic spinal cord injury, likely due to a developing immune deficiency syndrome. This, together with a somewhat contradictory development of autoimmunity in many patients, are two major components of the maladaptive systemic immune response. Although the local non-resolving inflammation in the lesioned spinal cord may lead to an antibody formation
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RBPome identification in egg-cell like callus of Arabidopsis Biol. Chem. (IF 3.7) Pub Date : 2023-09-28 Liping Liu, Jakob Trendel, Guojing Jiang, Yanhui Liu, Astrid Bruckmann, Bernhard Küster, Stefanie Sprunck, Thomas Dresselhaus, Andrea Bleckmann
RNA binding proteins (RBPs) have multiple and essential roles in transcriptional and posttranscriptional regulation of gene expression in all living organisms. Their biochemical identification in the proteome of a given cell or tissue requires significant protein amounts, which limits studies in rare and highly specialized cells. As a consequence, we know almost nothing about the role(s) of RBPs in
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HMGB1-RAGE axis contributes to myocardial ischemia/reperfusion injury via regulation of cardiomyocyte autophagy and apoptosis in diabetic mice Biol. Chem. (IF 3.7) Pub Date : 2023-09-28 De-Wei He, De-Zhao Liu, Xiao-Zhi Luo, Chuan-Bin Chen, Chuang-Hong Lu, Na Na, Feng Huang
Patients with acute myocardial infarction complicated with diabetes are more likely to develop myocardial ischemia/reperfusion (I/R) injury (MI/RI) during reperfusion therapy. Both HMGB1 and RAGE play important roles in MI/RI. However, the specific mechanisms of HMGB1 associated with RAGE are not fully clarified in diabetic MI/RI. This study aimed to investigate whether the HMGB1-RAGE axis induces
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Highlight: how to synthesize, assemble and regulate ribonucleoprotein-complexes. Biol. Chem. (IF 3.7) Pub Date : 2023-09-27 Herbert Tschochner
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Post-transcriptional gene silencing in a dynamic RNP world Biol. Chem. (IF 3.7) Pub Date : 2023-09-23 Simone Larivera, Julia Neumeier, Gunter Meister
MicroRNA (miRNA)-guided gene silencing is a key regulatory process in various organisms and linked to many human diseases. MiRNAs are processed from precursor molecules and associate with Argonaute proteins to repress the expression of complementary target mRNAs. Excellent work by numerous labs has contributed to a detailed understanding of the mechanisms of miRNA function. However, miRNA effects have
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Cell-type specific anti-cancerous effects of nitro-oleic acid and its combination with gamma irradiation Biol. Chem. (IF 3.7) Pub Date : 2023-09-15 Tomas Perecko, Jana Pereckova, Zuzana Hoferova, Martin Falk
Nitro-fatty acids (NFAs) are endogenous lipid mediators capable of post-translational modifications of selected regulatory proteins. Here, we investigated the anti-cancerous effects of nitro-oleic acid (NO2OA) and its combination with gamma irradiation on different cancer cell lines. The effects of NO2OA on cell death, cell cycle distribution, or expression of p21 and cyclin D1 proteins were analyzed
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A structural biology view on the enzymes involved in eukaryotic mRNA turnover Biol. Chem. (IF 3.7) Pub Date : 2023-09-14 Christina Krempl, Daniela Lazzaretti, Remco Sprangers
The cellular environment contains numerous ribonucleases that are dedicated to process mRNA transcripts that have been targeted for degradation. Here, we review the three dimensional structures of the ribonuclease complexes (Pan2-Pan3, Ccr4-Not, Xrn1, exosome) and the mRNA decapping enzymes (Dcp2, DcpS) that are involved in mRNA turnover. Structures of major parts of these proteins have been experimentally
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The archaeal Lsm protein from Pyrococcus furiosus binds co-transcriptionally to poly(U)-rich target RNAs Biol. Chem. (IF 3.7) Pub Date : 2023-09-14 Robert Reichelt, Tamara Rothmeier, Felix Grünberger, Sarah Willkomm, Astrid Bruckmann, Winfried Hausner, Dina Grohmann
Posttranscriptional processes in Bacteria include the association of small regulatory RNAs (sRNA) with a target mRNA. The sRNA/mRNA annealing process is often mediated by an RNA chaperone called Hfq. The functional role of bacterial and eukaryotic Lsm proteins is partially understood, whereas knowledge about archaeal Lsm proteins is scarce. Here, we used the genetically tractable archaeal hyperthermophile
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The promise of genetic screens in human in vitro brain models Biol. Chem. (IF 3.7) Pub Date : 2023-09-12 Julianne Beirute-Herrera, Beatriz López-Amo Calvo, Frank Edenhofer, Christopher Esk
Advances of in vitro culture models have allowed unprecedented insights into human neurobiology. At the same time genetic screening has matured into a robust and accessible experimental strategy allowing for the simultaneous study of many genes in parallel. The combination of both technologies is a newly emerging tool for neuroscientists, opening the door to identifying causal cell- and tissue-specific
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N6-methyladenosine-induced METTL1 promotes tumor proliferation via CDK4 Biol. Chem. (IF 3.7) Pub Date : 2023-09-11 Chunyan Zhang, Yuanbo Cui
N6-methyladenosine (m6A) and N7-methylguanosine (m7G) modification of RNA represent two major intracellular post-transcriptional regulation modes of gene expression. However, the crosstalk of these two epigenetic modifications in tumorigenesis remain poorly understood. Here, we show that m6A methyltransferase METTL3-mediated METTL1 promotes cell proliferation of head and neck squamous cell carcinoma
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The Zika virus infection remodels the expression of the synaptotagmin-9 secretory protein Biol. Chem. (IF 3.7) Pub Date : 2023-09-07 Santiago Leiva, Alejo Cantoia, Cintia Fabbri, Marina Bugnon Valdano, Victoria Luppo, María Alejandra Morales, Germán Rosano, Daniela Gardiol
The exact mechanisms involved in flaviviruses virions’ release and the specific secretion of viral proteins, such as the Non Structural protein-1 (NS1), are still unclear. While these processes might involve vesicular transport to the cell membrane, NS1 from some flaviviruses was shown to participate in viral assembly and release. Here, we assessed the effect of the Zika virus (ZIKV) NS1 expression
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Cytosolic RGG RNA-binding proteins are temperature sensitive flowering time regulators in Arabidopsis Biol. Chem. (IF 3.7) Pub Date : 2023-09-07 Andrea Bleckmann, Nicole Spitzlberger, Philipp Denninger, Hans F. Ehrnsberger, Lele Wang, Astrid Bruckmann, Stefan Reich, Philipp Holzinger, Jan Medenbach, Klaus D. Grasser, Thomas Dresselhaus
mRNA translation is tightly regulated by various classes of RNA-binding proteins (RBPs) during development and in response to changing environmental conditions. In this study, we characterize the arginine-glycine-glycine (RGG) motif containing RBP family of Arabidopsis thaliana representing homologues of the multifunctional translation regulators and ribosomal preservation factors Stm1 from yeast (ScStm1)
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Microtubules as a signal hub for axon growth in response to mechanical force Biol. Chem. (IF 3.7) Pub Date : 2023-09-07 Alessandro Falconieri, Allegra Coppini, Vittoria Raffa
Microtubules are highly polar structures and are characterized by high anisotropy and stiffness. In neurons, they play a key role in the directional transport of vesicles and organelles. In the neuronal projections called axons, they form parallel bundles, mostly oriented with the plus-end towards the axonal termination. Their physico-chemical properties have recently attracted attention as a potential
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Nanoscale organization of CaV2.1 splice isoforms at presynaptic terminals: implications for synaptic vesicle release and synaptic facilitation Biol. Chem. (IF 3.7) Pub Date : 2023-09-02 Lorenzo A. Cingolani, Agnes Thalhammer, Fanny Jaudon, Jessica Muià, Gabriele Baj
The distance between CaV2.1 voltage-gated Ca2+ channels and the Ca2+ sensor responsible for vesicle release at presynaptic terminals is critical for determining synaptic strength. Yet, the molecular mechanisms responsible for a loose coupling configuration of CaV2.1 in certain synapses or developmental periods and a tight one in others remain unknown. Here, we examine the nanoscale organization of
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The emerging role of ATP as a cosolute for biomolecular processes Biol. Chem. (IF 3.7) Pub Date : 2023-09-01 Alexander Hautke, Simon Ebbinghaus
ATP is an important small molecule that appears at outstandingly high concentration within the cellular medium. Apart from its use as a source of energy and a metabolite, there is increasing evidence for important functions as a cosolute for biomolecular processes. Owned to its solubilizing kosmotropic triphosphate and hydrophobic adenine moieties, ATP is a versatile cosolute that can interact with
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Optogenetics 2.0: challenges and solutions towards a quantitative probing of neural circuits Biol. Chem. (IF 3.7) Pub Date : 2023-08-31 Saleh Altahini, Isabelle Arnoux, Albrecht Stroh
To exploit the full potential of optogenetics, we need to titrate and tailor optogenetic methods to emulate naturalistic circuit function. For that, the following prerequisites need to be met: first, we need to target opsin expression not only to genetically defined neurons per se, but to specifically target a functional node. Second, we need to assess the scope of optogenetic modulation, i.e. the
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Rodent models for mood disorders – understanding molecular changes by investigating social behavior Biol. Chem. (IF 3.7) Pub Date : 2023-08-26 Patrick R. Reinhardt, Candy D. C. Theis, Georg Juckel, Nadja Freund
Mood disorders, including depressive and bipolar disorders, are the group of psychiatric disorders with the highest prevalence and disease burden. However, their pathophysiology remains poorly understood. Animal models are an extremely useful tool for the investigation of molecular mechanisms underlying these disorders. For psychiatric symptom assessment in animals, a meaningful behavioral phenotype
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Detection of a 7SL RNA-derived small non-coding RNA using Molecular Beacons in vitro and in cells Biol. Chem. (IF 3.7) Pub Date : 2023-08-26 Nina Weigert, Anna-Lena Schweiger, Jonas Gross, Marie Matthes, Selim Corbacioglu, Gunhild Sommer, Tilman Heise
Small non-coding RNAs (sncRNA) are involved in many steps of the gene expression cascade and regulate processing and expression of mRNAs by the formation of ribonucleoprotein complexes (RNP) such as the RNA-induced silencing complex (RISC). By analyzing small RNA Seq data sets, we identified a sncRNA annotated as piR-hsa-1254, which is likely derived from the 3′-end of 7SL RNA2 (RN7SL2), herein referred
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Characterization of the active site in the thiocyanate-forming protein from Thlaspi arvense (TaTFP) using EPR spectroscopy Biol. Chem. (IF 3.7) Pub Date : 2023-08-16 Haleh Hashemi Haeri, Nicola Schneegans, Daniela Eisenschmidt-Bönn, Wolfgang Brandt, Ute Wittstock, Dariush Hinderberger
Glucosinolates are plant thioglucosides, which act as chemical defenses. Upon tissue damage, their myrosinase-catalyzed hydrolysis yields aglucones that rearrange to toxic isothiocyanates. Specifier proteins such as thiocyanate-forming protein from Thlaspi arvense (TaTFP) are non-heme iron proteins, which capture the aglucone to form alternative products, e.g. nitriles or thiocyanates. To resolve the
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Intracellular spatially-targeted chemical chaperones increase native state stability of mutant SOD1 barrel Biol. Chem. (IF 3.7) Pub Date : 2023-08-09 Sara S. Ribeiro, David Gnutt, Salome Azoulay-Ginsburg, Zamira Fetahaj, Ella Spurlock, Felix Lindner, Damon Kuz, Yfat Cohen-Erez, Hanna Rapaport, Adrian Israelson, Arie-lev Gruzman, Simon Ebbinghaus
Amyotrophic lateral sclerosis (ALS) is a progressive neurological disorder with currently no cure. Central to the cellular dysfunction associated with this fatal proteinopathy is the accumulation of unfolded/misfolded superoxide dismutase 1 (SOD1) in various subcellular locations. The molecular mechanism driving the formation of SOD1 aggregates is not fully understood but numerous studies suggest that
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Highlight: integrative structural biology of dynamic macromolecular assemblies. Biol. Chem. (IF 3.7) Pub Date : 2023-08-08 Ralf Ficner
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Crosstalk between cholesterol and PIP2 in the regulation of Kv7.2/Kv7.3 channels Biol. Chem. (IF 3.7) Pub Date : 2023-08-08 Mayra Delgado-Ramírez, Ana Laura López-Serrano, Sergio Sánchez-Armass, Ulises Meza, Aldo A. Rodríguez-Menchaca
The activity of neuronal Kv7.2/Kv7.3 channels is critically dependent on PIP2 and finely modulated by cholesterol. Here, we report the crosstalk between cholesterol and PIP2 in the regulation of Kv7.2/Kv7.3 channels. Our results show that currents passing through Kv7.2/Kv7.3 channels in cholesterol-depleted cells, by acute application of methyl-β-cyclodextrin (MβCD), were less sensitive to PIP2 dephosphorylation
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The chromatin – triple helix connection Biol. Chem. (IF 3.7) Pub Date : 2023-07-28 Rodrigo Maldonado, Gernot Längst
Mammalian genomes are extensively transcribed, producing a large number of coding and non-coding transcripts. A large fraction of the nuclear RNAs is physically associated with chromatin, functioning in gene activation and silencing, shaping higher-order genome organisation, such as involvement in long-range enhancer–promoter interactions, transcription hubs, heterochromatin, nuclear bodies and phase
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Bayesian methods in integrative structure modeling Biol. Chem. (IF 3.7) Pub Date : 2023-07-28 Michael Habeck
There is a growing interest in characterizing the structure and dynamics of large biomolecular assemblies and their interactions within the cellular environment. A diverse array of experimental techniques allows us to study biomolecular systems on a variety of length and time scales. These techniques range from imaging with light, X-rays or electrons, to spectroscopic methods, cross-linking mass spectrometry
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Synthesis of the ribosomal RNA precursor in human cells: mechanisms, factors and regulation Biol. Chem. (IF 3.7) Pub Date : 2023-07-16 Julia L. Daiß, Joachim Griesenbeck, Herbert Tschochner, Christoph Engel
The ribosomal RNA precursor (pre-rRNA) comprises three of the four ribosomal RNAs and is synthesized by RNA polymerase (Pol) I. Here, we describe the mechanisms of Pol I transcription in human cells with a focus on recent insights gained from structure-function analyses. The comparison of Pol I-specific structural and functional features with those of other Pols and with the excessively studied yeast
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Structure and function of spliceosomal DEAH-box ATPases Biol. Chem. (IF 3.7) Pub Date : 2023-07-13 Marieke Enders, Piotr Neumann, Achim Dickmanns, Ralf Ficner
Splicing of precursor mRNAs is a hallmark of eukaryotic cells, performed by a huge macromolecular machine, the spliceosome. Four DEAH-box ATPases are essential components of the spliceosome, which play an important role in the spliceosome activation, the splicing reaction, the release of the spliced mRNA and intron lariat, and the disassembly of the spliceosome. An integrative approach comprising X-ray
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The DEAD-box RNA helicase Dbp5 is a key protein that couples multiple steps in gene expression Biol. Chem. (IF 3.7) Pub Date : 2023-07-12 Luisa Querl, Heike Krebber
Cell viability largely depends on the surveillance of mRNA export and translation. Upon pre-mRNA processing and nuclear quality control, mature mRNAs are exported into the cytoplasm via Mex67-Mtr2 attachment. At the cytoplasmic site of the nuclear pore complex, the export receptor is displaced by the action of the DEAD-box RNA helicase Dbp5. Subsequent quality control of the open reading frame requires
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The human long non-coding RNA LINC00941 and its modes of action in health and disease Biol. Chem. (IF 3.7) Pub Date : 2023-07-07 Eva Morgenstern, Markus Kretz
Long non-coding RNAs have gained attention in recent years as they were shown to play crucial roles in the regulation of cellular processes, but the understanding of the exact mechanisms is still incomplete in most cases. This is also true for long non-coding RNA LINC00941, which was recently found to be highly upregulated in various types of cancer influencing cell proliferation and metastasis. Initial
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Translation termination in human mitochondria – substrate specificity of mitochondrial release factors Biol. Chem. (IF 3.7) Pub Date : 2023-06-28 Franziska Nadler, Ricarda Richter-Dennerlein
Mitochondria are the essential players in eukaryotic ATP production by oxidative phosphorylation, which relies on the maintenance and accurate expression of the mitochondrial genome. Even though the basic principles of translation are conserved due to the descendance from a bacterial ancestor, some deviations regarding translation factors as well as mRNA characteristics and the applied genetic code
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Schwann cells in neuromuscular in vitro models Biol. Chem. (IF 3.7) Pub Date : 2023-06-26 Sarah Janice Hörner, Nathalie Couturier, Mathias Hafner, Rüdiger Rudolf
Neuromuscular cell culture models are used to investigate synapse formation and function, as well as mechanisms of de-and regeneration in neuromuscular diseases. Recent developments including 3D culture technique and hiPSC technology have propelled their ability to complement insights from in vivo models. However, most cultures have not considered Schwann cells, the glial part of NMJs. In the following
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Two are not enough: synthetic strategies and applications of unnatural base pairs Biol. Chem. (IF 3.7) Pub Date : 2023-06-25 Robert Dörrenhaus, Philip K. Wagner, Stephanie Kath-Schorr
Nucleic acid chemistry is a rapidly evolving field, and the need for novel nucleotide modifications and artificial nucleotide building blocks for diagnostic and therapeutic use, material science or for studying cellular processes continues unabated. This review focusses on the development and application of unnatural base pairs as part of an expanded genetic alphabet. Not only recent developments in
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Structure and phase separation of the C-terminal domain of RNA polymerase II Biol. Chem. (IF 3.7) Pub Date : 2023-06-19 Irina P. Lushpinskaia, David Flores-Solis, Markus Zweckstetter
The repetitive heptads in the C-terminal domain (CTD) of RPB1, the largest subunit of RNA Polymerase II (Pol II), play a critical role in the regulation of Pol II-based transcription. Recent findings on the structure of the CTD in the pre-initiation complex determined by cryo-EM and the novel phase separation properties of key transcription components offers an expanded mechanistic interpretation of
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Mycobacterial type VII secretion systems Biol. Chem. (IF 3.7) Pub Date : 2023-06-05 Nikolaos Famelis, Sebastian Geibel, Daan van Tol
Mycobacteria, such as the pathogen M. tuberculosis, utilize up to five paralogous type VII secretion systems to transport proteins across their cell envelope. Since these proteins associate in pairs that depend on each other for transport to a different extent, the secretion pathway to the bacterial surface remained challenging to address. Structural characterization of the inner-membrane embedded
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Molecular simulations of DEAH-box helicases reveal control of domain flexibility by ligands: RNA, ATP, ADP, and G-patch proteins. Biol. Chem. (IF 3.7) Pub Date : 2023-05-31 Robert A Becker,Jochen S Hub
DEAH-box helicases use the energy from ATP hydrolysis to translocate along RNA strands. They are composed of tandem RecA-like domains and a C-terminal domain connected by flexible linkers, and the activity of several DEAH-box helicases is regulated by cofactors called G-patch proteins. We used all-atom molecular dynamics simulations of the helicases Prp43, Prp22, and DHX15 in various liganded states
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Why do certain cancer cells alter functionality and fuse? Biol. Chem. (IF 3.7) Pub Date : 2023-05-29 Thomas Dittmar, Mareike Sieler, Ralf Hass
Cancer cell fusion represents a rare event. However, the surviving cancer hybrid cells after a post-hybrid selection process (PHSP) can overgrow other cancer cells by exhibiting a proliferation advantage and/or expression of cancer stem-like properties. Addition of new tumor properties during hetero-fusion of cancer cells e.g. with mesenchymal stroma-/stem-like cells (MSC) contribute to enhanced tumor
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Illuminating the brain-genetically encoded single wavelength fluorescent biosensors to unravel neurotransmitter dynamics Biol. Chem. (IF 3.7) Pub Date : 2023-05-29 Martin Kubitschke, Olivia A. Masseck
Understanding how neuronal networks generate complex behavior is one of the major goals of Neuroscience. Neurotransmitter and Neuromodulators are crucial for information flow between neurons and understanding their dynamics is the key to unravel their role in behavior. To understand how the brain transmits information and how brain states arise, it is essential to visualize the dynamics of neurotransmitters
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The Rauischholzhausen Transport Colloquium: membrane proteins from structure to function. Biol. Chem. (IF 3.7) Pub Date : 2023-05-29 Joachim Geyer,Eckhard Hofmann,Lutz Schmitt
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Molecular functions of RNA helicases during ribosomal subunit assembly Biol. Chem. (IF 3.7) Pub Date : 2023-05-26 Ali Khreiss, Katherine E. Bohnsack, Markus T. Bohnsack
During their biogenesis, the ribosomal subunits undergo numerous structural and compositional changes to achieve their final architecture. RNA helicases are a key driving force of such remodelling events but deciphering their particular functions has long been challenging due to lack of knowledge of their molecular functions and RNA substrates. Advances in the biochemical characterisation of RNA helicase
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The many faces of ribosome translocation along the mRNA: reading frame maintenance, ribosome frameshifting and translational bypassing Biol. Chem. (IF 3.7) Pub Date : 2023-05-24 Panagiotis Poulis, Frank Peske, Marina V. Rodnina
In each round of translation elongation, the ribosome translocates along the mRNA by precisely one codon. Translocation is promoted by elongation factor G (EF-G) in bacteria (eEF2 in eukaryotes) and entails a number of precisely-timed large-scale structural rearrangements. As a rule, the movements of the ribosome, tRNAs, mRNA and EF-G are orchestrated to maintain the exact codon-wise step size. However
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Membrane-anchored substrate binding proteins are deployed in secondary TAXI transporters Biol. Chem. (IF 3.7) Pub Date : 2023-05-24 Anja Roden, Melanie K. Engelin, Klaas M. Pos, Eric R. Geertsma
Substrate-binding proteins (SBPs) are part of solute transport systems and serve to increase substrate affinity and uptake rates. In contrast to primary transport systems, the mechanism of SBP-dependent secondary transport is not well understood. Functional studies have thus far focused on Na+-coupled Tripartite ATP-independent periplasmic (TRAP) transporters for sialic acid. Herein, we report the