- Cardiomyopathy and Myosin Studies
- Chemical Analysis and Environmental Impact
- Cellular Mechanics and Interactions
- Skin and Cellular Biology Research
- Polysaccharides and Plant Cell Walls
- Water Treatment and Disinfection
- Enzyme Structure and Function
- Cellular transport and secretion
- Trypanosoma species research and implications
- Genetic Neurodegenerative Diseases
- Ion channel regulation and function
- Cardiovascular Effects of Exercise
- Fluoride Effects and Removal
- Toxoplasma gondii Research Studies
- Arsenic contamination and mitigation
- Nail Diseases and Treatments
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Protein Structure and Dynamics
- DNA Repair Mechanisms
- Force Microscopy Techniques and Applications
- Nuclear Structure and Function
- Cardiac electrophysiology and arrhythmias
- Genetics and Physical Performance
- Mosquito-borne diseases and control
Vienna Biocenter
2004-2024
University of Vienna
2012-2024
Max Perutz Labs
2013-2024
Ruhr University Bochum
2021
St. Marien Hospital
2021
University of Ljubljana
2021
University of Bonn
2021
Slovak Academy of Sciences
2004
The spectrin superfamily of proteins plays key roles in assembling the actin cytoskeleton various cell types, crosslinks filaments, and acts as scaffolds for assembly large protein complexes involved structural integrity mechanosensation, well signaling. α-actinins particular are major crosslinkers muscle Z-disks, focal adhesions, stress fibers. We report a complete high-resolution structure 200 kDa α-actinin-2 dimer from striated explore its functional implications on biochemical cellular...
The trypanosomes are a family of parasitic protists which the African trypanosome, Trypanosoma brucei, is best characterized. complex and highly ordered cytoskeleton T. brucei has been shown to play vital roles in its biology but remains difficult study, large part owing intractability constituent proteins. Existing methods protein identification, such as bioinformatic analysis, generation monoclonal antibody panels, proteomics, affinity purification, yeast two-hybrid screens, all have...
Guanidine is a chemically stable nitrogen compound that excreted in human urine and widely used manufacturing of plastics, as flame retardant component propellants, well known protein denaturant biochemistry
Chlorite dismutase (Cld) is a unique heme enzyme catalyzing the conversion of ClO(2)(-) to Cl(-) and O(2). Cld usually found in perchlorate- or chlorate-reducing bacteria but was also recently identified nitrite-oxidizing bacterium genus Nitrospira. Here we characterized novel Cld-like protein from chemolithoautotrophic nitrite oxidizer Nitrobacter winogradskyi which significantly smaller than all previously known chlorite dismutases. Its three-dimensional (3D) crystal structure revealed...
Significance Muscle is the tissue in our body experiencing most extreme mechanical forces. The mechanism of active force generation has been investigated for more than 50 y and fairly well understood. However, despite its physiological significance, it still unknown what linkages hold together muscle machinery under passive stretching In this paper, we show with direct single-molecule measurements that an array titin/α-actinin bonds composes a dynamic network can provide stable anchoring,...
Plectin, a large and widely expressed cytolinker protein, is composed of several subdomains that harbor binding sites for variety different interaction partners. A canonical actin‐binding domain (ABD) comprising two calponin homology domains (CH1 CH2) located in proximity to its amino terminus. However, the ABD plectin unique among proteins as it form distinct, isoform‐specific versions. We have determined three‐dimensional structure distinct crystalline forms one versions (pleABD/2α) from...
The detachment of epithelial cells from the basal matrix during wound healing and differentiation keratinocytes requires disassembly hemidesmosomal multiprotein adhesion complex. Integrin α6β4-plectin interaction plays a major role in formation hemidesmosomes, thus mechanisms regulating this should be critical also for process. Here we show that particular plectin isoform (1a) interacts with Ca2+-sensing protein calmodulin Ca2+-dependent manner. As result interaction, binding...
Chlorite dismutases (Clds) are heme b containing oxidoreductases that convert chlorite to chloride and molecular oxygen. In order elucidate the role of conserved cavity residues in catalysis this reaction comprehensive mutational biochemical analyses Cld from "Candidatus Nitrospira defluvii" (NdCld) were performed. Particularly, point mutations cavity-forming R173, K141, W145, W146, E210 The effect manipulation 12 single double mutants was probed by UV-vis spectroscopy,...
Chlorite dismutases (Clds) are heme b-containing oxidoreductases that convert chlorite to chloride and dioxygen. In this work, the thermodynamics of one-electron reduction ferric high-spin forms six-coordinate low-spin cyanide adducts enzymes from Nitrobacter winogradskyi (NwCld) Candidatus "Nitrospira defluvii" (NdCld) were determined through spectroelectrochemical experiments. These proteins belong two phylogenetically separated lineages differ in subunit (21.5 26 kDa, respectively)...
MORN (Membrane Occupation and Recognition Nexus) repeat proteins have a wide taxonomic distribution, being found in both prokaryotes eukaryotes. Despite this ubiquity, they remain poorly characterised at structural functional level compared to other common repeats. In terms, are often assumed be lipid-binding modules that mediate membrane targeting. We addressed putative activity by focusing on protein composed solely of repeats— Trypanosoma brucei MORN1. Surprisingly, no evidence for...
To determine whether a new indel mutation in the dimerization domain of filamin C (FLNc) causes hereditary myopathy with protein aggregation muscle fibers, we clinically and molecularly studied German family autosomal dominant myofibrillar (MFM).We performed mutational analysis 3 generations, histopathology, proteomic studies IM aggregates. Functional consequences FLNC were investigated interaction transfection biophysics molecular analysis.Eight patients revealed clinical features slowly...
Sarcomeric proteins FATZ-1 and α-actinin-2 associate in a tight fuzzy complex, which forms phase-separated condensates.
Chlorite dismutases (Cld) are unique heme b containing oxidoreductases that convert chlorite to chloride and dioxygen. Recent phylogenetic structural analyses demonstrated these metalloproteins significantly differ in oligomeric subunit structure. Here we have analyzed two representatives of phylogenetically separated lineages, namely pentameric Cld from Candidatus “Nitrospira defluvii” dimeric Nitrobacter winogradskyi having a similar enzymatic activity at room temperature. By application...
Significance Actin is one of the most abundant proteins in eukaryotic cells. filaments together with a large number actin-binding are critical players many cellular functions, ranging from cell motility and muscle contraction to maintenance shape transcription regulation. α-Actinin—a member spectrin superfamily—is an archetypical F-actin–binding –bundling protein. It known that Ca 2+ inhibits α-actinin capacity bundle F-actin. We present structure -regulated propose mechanism for its uncover...
Sarcomeres, the basic contractile units of striated muscle cells, contain arrays thin (actin) and thick (myosin) filaments that slide past each other during contraction. The Ig-like domain-containing protein myotilin provides structural integrity to Z-discs—the boundaries between adjacent sarcomeres. Myotilin binds Z-disc components, including F-actin α-actinin-2, but molecular mechanism binding implications these interactions on are still elusive. To illuminate them, we used a combination...
The S -adenosyl-L-methionine (SAM)-dependent methyltransferase CcbJ from Streptomyces caelestis catalyzes one of the final steps in biosynthesis antibiotic celesticetin, methylation N atom its proline moiety, which greatly enhances activity antibiotic. Since several celesticetin variants exist, this enzyme may be able to act on a variety substrates. structures determined by MAD phasing at 3.0 Å resolution, native form 2.7 resolution and complex with -adenosyl-L-homocysteine (SAH) 2.9 are...
Abstract Cardiomyopathies, diseases of the heart muscle, are a leading cause failure. An increasing proportion cardiomyopathies have been associated with specific genetic changes, such as mutations in FLNC , gene that codes for filamin C. Altogether, more than 300 variants identified patients, including number single point mutations. However, role significant these remains unknown. Here, we conducted comprehensive analysis, starting from clinical data led to identification new pathogenic and...
To study the mechanisms involved in maintenance of a linear mitochondrial genome we investigated biochemical properties recombination protein Mgm101 from Candida parapsilosis. We show that CpMgm101 complements defects associated with Saccharomyces cerevisiae mgm101–1ts mutation and it is present both nucleus nucleoids C. Unlike its S. counterpart, entire nucleoid population able to bind broad range DNA substrates non-sequence specific manner. also catalyze strand annealing D-loop formation....