A5072809208- Cardiomyopathy and Myosin Studies
- Enzyme Structure and Function
- RNA and protein synthesis mechanisms
- Biochemical and Molecular Research
- Protein Structure and Dynamics
- Force Microscopy Techniques and Applications
- Cellular Mechanics and Interactions
- Muscle Physiology and Disorders
- Genetic Neurodegenerative Diseases
- Enzyme Production and Characterization
- Glycosylation and Glycoproteins Research
- Genetics, Aging, and Longevity in Model Organisms
- Amino Acid Enzymes and Metabolism
- RNA Research and Splicing
- Monoclonal and Polyclonal Antibodies Research
- Cancer Research and Treatments
- Bacteriophages and microbial interactions
- Advanced Electron Microscopy Techniques and Applications
- Cell Adhesion Molecules Research
- Polysaccharides and Plant Cell Walls
- Neuroscience and Neuropharmacology Research
- Peptidase Inhibition and Analysis
- Molecular Junctions and Nanostructures
- Ubiquitin and proteasome pathways
- Cellular transport and secretion
University of Konstanz
2016-2025
University of Liverpool
2011-2023
University of Basel
2002-2015
University of Göttingen
2012
University of York
2011
Center for Nanoscale Science and Technology
2010
Heidelberg University
2008
University Hospital Heidelberg
2008
University Medical Centre Mannheim
2008
European Molecular Biology Laboratory
2002-2006
The development of resistance to insecticides has become a classic exemplar evolution occurring within human time scales. In this study we demonstrate how DDT in the major African malaria vector Anopheles gambiae is result both target-site mechanisms that have introgressed between incipient species (the M- and S-molecular forms) allelic variants DDT-detoxifying enzyme. Sequencing detoxification enzyme, Gste2, from resistant susceptible strains An. gambiae, revealed non-synonymous...
Protein ab initio models predicted from sequence data alone can enable the elucidation of crystal structures by molecular replacement. However, calculation such is typically computationally expensive. Here, a computational pipeline based on clustering and truncation cheaply obtained for preparation structure ensembles described. Clustering used to select quantitatively predict their local accuracy, allowing rational inaccurate regions. The resulting ensembles, with or without rapidly added...
Lysine degradation has remained elusive in many organisms including Escherichia coli. Here we report catabolism of lysine to succinate E. coli involving glutarate and L-2-hydroxyglutarate as intermediates. We show that CsiD acts an α-ketoglutarate-dependent dioxygenase catalysing hydroxylation L-2-hydroxyglutarate. is found widespread bacteria. present crystal structures complex with glutarate, succinate, the inhibitor N-oxalyl-glycine, demonstrating strong discrimination between...
Striated muscle undergoes remodelling in response to mechanical and physiological stress, but little is known about the integration of such varied signals myofibril.The interaction elastic kinase region from sarcomeric titin (A168-M1) with autophagy receptors Nbr1/p62 MuRF E3 ubiquitin ligases well suited link mechanosensing trophic myofibril.To investigate mechanisms signal cross-talk at this node, we elucidated its 3D structure, analysed stretch using steered molecular dynamics simulations...
The crystal structure of the α-amylase from hyperthermophilic archaeon <i>Pyrococcus woesei</i> was solved in presence three inhibitors: acarbose, Tris, and zinc. In absence exogenous metals, this bound 1 4 molar eq zinc calcium, respectively. reveals a novel, activating, two-metal (Ca,Zn)-binding site second inhibitory zinc-binding that is found −1 sugar-binding pocket within active site. data resolve apparent paradox between requirement for catalytic activity its strong effect when added...
Titin forms an intrasarcomeric filament system in vertebrate striated muscle, which has elastic and signaling properties is thereby central to mechanotransduction. Near its C-terminus directly preceding a kinase domain, titin contains conserved pattern of Ig FnIII modules (Ig(A168)-Ig(A169)-FnIII(A170), hereby A168-A170) that recruits the E3 ubiquitin-ligase MuRF-1 filament. This interaction thought regulate myofibril turnover trophic state muscle. We have elucidated crystal structure...
Myofibril elasticity, critical to muscle function, is dictated by the intrasarcomeric filament titin, which acts as a molecular spring. To date, events underlying mechanics of folded titin chain remain largely unknown. We have elucidated crystal structure 6-Ig fragment I65–I70 from elastic I-band fraction and validated its conformation in solution using small angle x-ray scattering. The long-range properties been visualized electron microscopy on 19-Ig modeled for full skeletal tandem....
Striated muscle tissues undergo adaptive remodelling in response to mechanical load. This process involves the myofilament titin and, specifically, its kinase domain (TK; kinase) that translates signals into regulatory pathways of gene expression myofibril. TK mechanosensing appears mediated by a C-terminal tail (CRD) sterically inhibits active site. Allegedly, stretch-induced unfolding this during function releases inhibition and leads catalytic activation. However, cellular pathway is...
Abstract Fluorine labelling represents one promising approach to study proteins in their native environment due efficient suppressing of background signals. Here, we systematically probe inherent thermodynamic and structural characteristics the Cold shock protein B from Bacillus subtilis ( Bs CspB) upon fluorine labelling. A sophisticated combination fluorescence NMR experiments has been applied elucidate potential perturbations insertion into protein. We show that single phenylalanine or...
The nuclear receptor liver homolog-1 (LRH-1) has been shown to promote apoptosis resistance in various tissues and disease contexts; however, its role cell death remains unexplored. Hepatocyte-specific deletion of LRH-1 causes mild steatosis inflammation but unexpectedly shields female mice from tumor necrosis factor (TNF)-induced hepatocyte associated hepatitis. LRH-1-deficient hepatocytes show markedly attenuated estrogen alpha elevated κB (NF-κB) activity, while overexpression inhibits...
The B-box motif is the defining feature of TRIM family proteins, characterized by a RING finger−B-box−coiled coil tripartite fold. We have elucidated crystal structure 2 (B2) from MuRF1, protein that supports wide variety interactions in sarcomere and regulates trophic state striated muscle tissue. MuRF1 B2 coordinates two zinc ions through cross-brace α/β-topology typical members finger superfamily. However, it self-associates into dimers with high affinity. dimerization pattern mediated...