A5072448300- Enzyme Catalysis and Immobilization
- RNA Research and Splicing
- Microbial Metabolic Engineering and Bioproduction
- Cytokine Signaling Pathways and Interactions
- Genomics and Chromatin Dynamics
- RNA and protein synthesis mechanisms
- Cannabis and Cannabinoid Research
- Lipid metabolism and biosynthesis
- Analytical Chemistry and Chromatography
- Ubiquitin and proteasome pathways
- interferon and immune responses
- Plant biochemistry and biosynthesis
- DNA Repair Mechanisms
- RNA regulation and disease
- Natural Antidiabetic Agents Studies
- Diet, Metabolism, and Disease
- RNA modifications and cancer
- Protein Degradation and Inhibitors
- Quinazolinone synthesis and applications
- Diabetes Management and Research
- NF-κB Signaling Pathways
- Advanced Proteomics Techniques and Applications
- Peptidase Inhibition and Analysis
- Biochemical and Molecular Research
- Diet and metabolism studies
Max Planck Institute for Multidisciplinary Sciences
2022-2024
Max Planck Institute for Biophysical Chemistry
2018-2021
Max Planck Society
2019
University of Leicester
2019
European Molecular Biology Laboratory
2017-2018
University of Graz
2010-2016
Institut Pasteur
2011
Université de Lorraine
2011
Significance Cytokines interact with their receptors and activate JAK–STAT signaling pathways that lead to changes in gene expression. In mammals, there are seven STATs have arisen due duplication genetic drift. similar DNA binding specificity, how individual subfunctionalized regulate very specific cytokine responses cells is poorly understood. Here we describe X-ray structures show one STAT family member, STAT2, specifically pairs a member of the IRF transcription factors, IRF9. Despite...
Monoacylglycerols (MAGs) are short-lived intermediates of glycerolipid metabolism. Specific molecular species, such as 2-arachidonoylglycerol, which is a potent activator cannabinoid receptors, may also function lipid signaling molecules. In mammals, enzymes hydrolyzing MAG to glycerol and fatty acids, resembling the final step in lipolysis, or esterifying diacylglycerol, well known; however, despite high level conservation corresponding activities yeast have not been characterized yet. Here...
Monoacylglycerol lipases (MGLs) play an important role in lipid catabolism across all kingdoms of life by catalyzing the release free fatty acids from monoacylglycerols. The three-dimensional structures human and a bacterial MGL were determined only recently as first members this lipase family. In addition to α/β-hydrolase core, they showed unexpected structural similarities even cap region. Nevertheless, basis for substrate binding conformational changes MGLs is poorly understood. Here, we...
Monoacylglycerol lipases (MGLs) catalyse the hydrolysis of monoacylglycerol into free fatty acid and glycerol. MGLs have been identified throughout all genera life adopted different substrate specificities depending on their physiological role. In humans, MGL plays an integral part in lipid metabolism affecting energy homeostasis, signalling processes cancer cell progression. bacteria, degrade short-chain monoacylglycerols which are otherwise toxic to organism. We report crystal structures...
The serine/threonine kinase TBK1 (TANK-binding 1) and its homologue IKKε are noncanonical members of the inhibitor nuclear factor κB (IκB) family. These kinases play important roles in multiple cellular pathways and, particular, inflammation. Herein, we describe our investigations on a family benzimidazoles identification potent highly selective TBK1/IKKε BAY-985. BAY-985 inhibits phosphorylation interferon regulatory 3 displays antiproliferative efficacy melanoma cell line SK-MEL-2 but...
Abstract RNA polymerase II (Pol II) carries out transcription of both protein-coding and non-coding genes. Whereas Pol initiation at genes has been studied in detail, genes, such as small nuclear (snRNA) is less well understood the structural level. Here, we study snRNA gene promoters show that snRNA-activating protein complex (SNAPc) enables DNA opening independent TFIIE TFIIH vitro. We then resolve cryo-EM structures SNAPc-containing IIpre-initiation (PIC) assembled on U1 U5 promoters. The...
Monoglyceride lipases (MGLs) are a group of α/β-hydrolases that catalyze the hydrolysis monoglycerides (MGs) into free fatty acids and glycerol. This reaction serves different physiological functions, namely in last step phospholipid triglyceride degradation, mammalian endocannabinoid arachidonic acid metabolism, detoxification processes microbes. Previous crystal structures MGLs from humans bacteria revealed conformational plasticity cap region this protein gave insight substrate binding....
Recent advances in cryo-electron microscopy have led to multiple structures of Mediator complex with the RNA polymerase II (Pol II) transcription initiation machinery. As a result we now hold hands near-complete both yeast and human complexes better understanding their interactions Pol pre-initiation (PIC). Herein, provide summary recent achievements discuss implications for future studies its role gene regulation.
Abstract The mechanisms underlying the initiation and elongation of RNA polymerase II (Pol II) transcription are well-studied, whereas termination remains poorly understood. Here we analyze mechanism polyadenylation-independent Pol mediated by yeast Sen1 helicase. Cryo-electron microscopy structures two pretermination intermediates show that binds to uses its adenosine triphosphatase activity pull on exiting in 5′ direction. This is predicted push forward, induce an unstable...
The protein Yju3p is the orthologue of monoglyceride lipases in yeast Saccharomyces cerevisiae. A soluble variant this lipase termed s-Yju3p (38.3 kDa) was generated and purified to homogeneity by affinity size-exclusion chromatography. crystallized a vapour-diffusion setup at 293 K complete data set collected 2.4 Å resolution. crystal form orthorhombic (space group P212121), with unit-cell parameters = 77.2, b 108.6, c 167.7 Å. asymmetric unit contained four molecules solvent content 46.4%.
Mediator is a conserved coactivator that enables regulated transcription initiation from eukaryotic protein-coding genes 1-3 . recruited by transcriptional activators and binds the pre-initiation complex (PIC) to stimulate RNA polymerase II (Pol II) phosphorylation promoter escape 1-6 Here we prepare 20-subunit recombinant human Mediator, reconstitute 50-subunit Mediator-PIC complex, resolve structure cryo-EM at an overall resolution of 4.5 Å. with its head module Pol stalk general factors...
Summary Cytokine signalling is mediated by the activation of distinct sets structurally homologous JAK and STAT molecules, which control nuclear gene expression cell fate. A significant expansion in regulatory repertoire controlled JAK/STAT has arisen selective interaction STATs with IRF transcription factors. Type I interferons (IFN), major antiviral cytokines, trigger formation ISGF3 complex containing STAT1, STAT2 IRF9. regulates IFN–stimulated genes (ISGs). assembly depends on between...
SessionsC783 of 2.97 Å 3 /Da and a solvent content 59%.The crystal structure has been determined by molecular replacement.The current model was refined at 2.6 resolution to an R-factor 23.8% (R free = 31.6%).In crystals, LsAspR adopts homodimeric form.The subunit consists two domains: the N-terminal domain (residues 1-104 216-234) C-terminal 105-215).In each domain, central four-stranded parallel β-sheet is flanked six αhelices.The spatial arrangement strictly conserved residues Cys84 Cys196...