Research Area C - Publications 2017

Cell, 171, 1–15, https://doi.org/10.1016/j.cell.2017.09.039
Cell, online article

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Detection of cytosolic DNA constitutes a central event in the context of numerous infectious and sterile inflammatory conditions. Recent studies have uncovered a bipartite mode of cytosolic DNA recognition, in which the cGAS-STING axis triggers antiviral immunity, whereas AIM2 triggers inflammasome activation. Here, we show that AIM2 is dispensable for ...

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Nature, 549, 394–398, doi:10.1038/nature23890
Nature, online article

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Cytosolic DNA arising from intracellular pathogens triggers a powerful innate immune response. It is sensed by cyclic GMP–AMP synthase (cGAS), which elicits the production of type I interferons by generating the second messenger 2′3′-cyclic-GMP–AMP (cGAMP). Endogenous nuclear or mitochondrial DNA can also be sensed by cGAS under certain conditions, resulting in ...

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J. Biol. Chem., (2017) 292(41), 17073–17083, DOI 10.1074/jbc.M117.797829
J. Biol. Chem., online article

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The eukaryotic Hsp90 chaperone machinery comprises many co-chaperones and regulates the conformation of hundreds of cytosolic client proteins. Therefore, it is not surprising that the Hsp90 machinery has become an attractive therapeutic target for diseases such as cancer. The compounds used so far to target this machinery affect the entire Hsp90 system. However, ...

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Nature Communications, volume 8, Article number: 266, doi:10.1038/s41467-017-00366-1
Nature Communications, online article

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The immune system plays a major role in human health and disease, and understanding genetic causes of interindividual variability of immune responses is vital. Here, we isolate monocytes from 134 genotyped individuals, stimulate these cells with three defined microbe-associated molecular patterns (LPS, MDP, and 5′-ppp-dsRNA), and profile the transcriptomes at ...

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Chemistry - A European Journal, Volume23, Issue57, Pages 14267-14277, https://doi.org/10.1002/chem.201702423
Chemistry, online article

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Fluorescence‐based techniques are widely used to study biomolecular conformations, intra‐ and intermolecular interactions, and conformational dynamics of macromolecules. Especially for fluorescence‐based single‐molecule experiments, the choice of the fluorophore and labeling position are highly important. In this work, we studied the biophysical and structural ...

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PLoS ONE, 12(7): e0181799, https://doi.org/10.1371/journal.pone.0181799
PLoS ONE, online article

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Little structural information is available so far on amyloid fibrils consisting of immunoglobulin light chains. It is not understood which features of the primary sequence of the protein result in fibril formation. We report here MAS solid-state NMR studies to identify the structured core of κ-type variable domain light chain fibrils. The core contains residues ...

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Scientific Reports, 7, Article number: 5393,  doi:10.1038/s41598-017-05821-z
Scientific Reports, online article

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NMR spectroscopy is a powerful technique to study ribonucleic acids (RNAs) which are key players in a plethora of cellular processes. Although the NMR toolbox for structural studies of RNAs expanded during the last decades, they often remain challenging. Here, we show that solvent paramagnetic relaxation enhancements (sPRE) induced by the soluble, paramagnetic ...

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Angewandte Chemie International Edition, DOI: 10.1002/anie.201702904
Angewandte Chemie International Edition, online article

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Multi-domain proteins play critical roles in fine-tuning essential processes in cellular signaling and gene regulation. Typically, multiple globular domains that are connected by flexible linkers undergo dynamic rearrangements upon binding to protein, DNA or RNA ligands. RNA binding proteins (RBPs) represent an important class of multi-domain proteins, which ...

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Microbial Cell, Vol. 4, No. 7, pp. 229 - 232; DOI: 10.15698/mic2017.07.581
Microbial Cell, online article

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Vector-borne trypanosomatid parasite infections in tropical and sub-tropical countries constitute a major threat to humans and livestock. Trypanosoma brucei parasites are transmitted by tsetse fly and lead to African sleeping sickness in humans and Nagana in cattle. In Latin American countries, Trypanosoma cruzi infections spread by triatomine kissing bugs lead ...

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Scientific Reports, 7, Article number: 1051, doi:10.1038/s41598-017-01031-9
Scientific Reports, online article

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The transmembrane DNA-binding protein CadC of E. coli, a representative of the ToxR-like receptor family, combines input and effector domains for signal sensing and transcriptional activation, respectively, in a single protein, thus representing one of the simplest signalling systems. At acidic pH in a lysine-rich environment, CadC activates the transcription of ...

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J. Biol. Chem. (2017) 292(22) 9000–9009, doi: 10.1074/jbc.R117.788398 jbc.R117.788398
J. Biol. Chem., online article

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RIG-I-like receptors (RLRs) are cytosolic innate immune sensors that detect pathogenic RNA and induce a systemic antiviral response. During the last decade many studies focused on their molecular characterization and the identification of RNA agonists. Thereby it became more and more clear that RLR activation needs to be carefully regulated, since constitutive ...

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Science, Vol. 355, Issue 6332, pp. 1416-1420, DOI: 10.1126/science.aal1807
Science, online article
 

 

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The parasitic protists of the Trypanosoma genus infect humans and domestic mammals, causing severe mortality and huge economic losses. The most threatening trypanosomiasis is Chagas disease, affecting up to 12 million people in the Americas. We report a way to selectively kill Trypanosoma by blocking glycosomal/peroxisomal import that depends on the PEX14-PEX5 ...

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Methods, Volumes 118–119, Pages 119-136, https://doi.org/10.1016/j.ymeth.2017.03.015
Methods, online article

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Recent advances in RNA sequencing technologies have greatly expanded our knowledge of the RNA landscape in cells, often with spatiotemporal resolution. These techniques identified many new (often non-coding) RNA molecules. Large-scale studies have also discovered novel RNA binding proteins (RBPs), which exhibit single or multiple RNA binding domains (RBDs) for ...

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Nature Communications, 8, Article number: 14635 (2017), doi:10.1038/ncomms14635
Nature Communications, online article

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The transport of peroxisomal membrane proteins (PMPs) requires the soluble PEX19 protein as chaperone and import receptor. Recognition of cargo PMPs by the C-terminal domain (CTD) of PEX19 is required for peroxisome biogenesis in vivo. Farnesylation at a C-terminal CaaX motif in PEX19 enhances the PMP interaction, but the underlying molecular mechanisms are ...

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GLIA, DOI: 10.1002/glia.23115
GLIA, online article

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Glia play crucial roles in the development and homeostasis of the nervous system. While the GLIA in the Drosophila embryo have been well characterized, their study in the adult nervous system has been limited. Here, we present a detailed description of the glia in the adult nervous system, based on the analysis of some 500 glial drivers we identified within a ...

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Scientific Reports, volume 7, Article number: 41515, doi:10.1038/srep41515
Scientific Reports, online article

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Antibody light chain amyloidosis is a rare disease caused by fibril formation of secreted immunoglobulin light chains (LCs). The huge variety of antibody sequences puts a serious challenge to drug discovery. The green tea polyphenol epigallocatechin-3-gallate (EGCG) is known to interfere with fibril formation in general. Here we present solution- and solid-state ...

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J. Am. Chem. Soc., Just Accepted Manuscript, DOI: 10.1021/jacs.6b09619
J. Am. Chem. Soc., online article

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Fibrillar aggregates of Aβ and Tau in the brain are the major hallmarks of Alzheimer’s disease. Most Tau fibers have a twisted appearance but the twist can be variable and even absent. This ambiguity, which has also been associated with different phenotypes of tauopathies, has led to controversial assumptions about fibril constitution, and it is unclear to-date ...

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Biology Open, Online ISSN 2046-6390, doi: 10.1242/bio.020669
Biology Open, online article

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During development, many epithelia are formed by a mesenchymal-epithelial transition (MET). Here, we examine the major stages and underlying mechanisms of MET during blood-brain barrier formation in Drosophila. We show that contact with the basal lamina is essential for the growth of the barrier-forming subperineurial glia (SPG). Septate junctions (SJs), which ...

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Nature Structural & Molecular Biology, 24, 152–161, doi:10.1038/nsmb.3351
Nature Structural & Molecular Biology, online article

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mRNA localization is an essential mechanism of gene regulation and is required for processes such as stem-cell division, embryogenesis and neuronal plasticity. It is not known which features in the cis-acting mRNA localization elements (LEs) are specifically recognized by motor-containing transport complexes. To the best of our knowledge, no high-resolution ...

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Scientific Reports, 7, Article number: 39805, doi:10.1038/srep39805
Scientific Reports, online article

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Integrins, a diverse class of heterodimeric cell surface receptors, are key regulators of cell structure and behaviour, affecting cell morphology, proliferation, survival and differentiation. Consequently, mutations in specific integrins, or their deregulated expression, are associated with a variety of diseases. In the last decades, many integrin-specific ...

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J Mol Biol, Volume 430, Issue 2, Pages 133-141, https://doi.org/10.1016/j.jmb.2017.11.013
J Mol Biol., online article

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NLRP3 is the most studied inflammasome sensor due to its crucial involvement in sterile and infection-triggered inflammation. Although its molecular mode of activation remains to be defined, it is well established that low intracellular potassium concentrations result in its activation. This functionality allows the classical NLRP3 pathway to serve as a highly ...

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