A5073020411- Monoclonal and Polyclonal Antibodies Research
- Click Chemistry and Applications
- Advanced biosensing and bioanalysis techniques
- Chemical Synthesis and Analysis
- Receptor Mechanisms and Signaling
- Immune Response and Inflammation
- RNA regulation and disease
- Peptidase Inhibition and Analysis
- interferon and immune responses
- Radiopharmaceutical Chemistry and Applications
- Glycosylation and Glycoproteins Research
- Advanced Fluorescence Microscopy Techniques
- Neuropeptides and Animal Physiology
- Drug Transport and Resistance Mechanisms
- Biochemical and Structural Characterization
- Cancer-related Molecular Pathways
- Sphingolipid Metabolism and Signaling
- DNA and Nucleic Acid Chemistry
- Fluorine in Organic Chemistry
- Integrated Circuits and Semiconductor Failure Analysis
- Tryptophan and brain disorders
- Epigenetics and DNA Methylation
- Inflammasome and immune disorders
- Trace Elements in Health
- Advanced Electron Microscopy Techniques and Applications
University of Bonn
2020-2024
University Hospital Bonn
2020-2023
Goethe University Frankfurt
2018-2022
The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread, with devastating consequences. For passive immunization efforts, nanobodies have size and cost advantages over conventional antibodies. In this study, we generated four neutralizing that target the receptor binding domain of SARS-CoV-2 spike protein. We used x-ray crystallography cryo-electron microscopy define two distinct epitopes. On basis these structures, engineered multivalent more...
Tripartite ATP-independent periplasmic (TRAP) transporters are found widely in bacteria and archaea consist of three structural domains, a soluble substrate-binding protein (P-domain), two transmembrane domains (Q- M-domains). HiSiaPQM its homologs TRAP for sialic acid essential host colonization by pathogenic bacteria. Here, we reconstitute HiSiaQM into lipid nanodiscs use cryo-EM to reveal the structure transporter. It is composed 16 helices that unexpectedly structurally related...
Abstract Cyclin-dependent kinase 7 (Cdk7) is required in cell-cycle and transcriptional regulation owing to its function as both a CDK-activating (CAK) part of transcription factor TFIIH. Cdk7 forms active complexes by associating with Cyclin H Mat1, regulated two phosphorylations the activation segment (T loop): canonical activating modification at T170 another S164. Here we report crystal structure human Cdk7/Cyclin H/Mat1 complex containing T-loop phosphorylations. Whereas pT170...
The photostability of fluorescent labels comprises one the main limitations in single-molecule fluorescence (SMF) and super-resolution imaging. An attractive strategy to increase organic fluorophores relies on their coupling photostabilizers, e.g., triplet excited state quenchers, rendering self-healing dyes. Herein we report properties trisNTA-Alexa647 (NTA, N-nitrilotriacetic acid). Primarily designed specifically label biomolecules containing an oligohistidine tag, hypothesized that...
Small chemical/biological interaction pairs are at the forefront in tracing protein function and high signal-to-background ratios cellular pathways. However, optimal design of scaffold, linker, chelator head still deserve systematic investigation to achieve highest affinity kinetic stability for vitro especially applications. We report on a library N-nitrilotriacetic acid (NTA)-based multivalent heads (MCHs) built linear, cyclic, dendritic scaffolds compare these with regard their binding...
How membrane proteins oligomerize determines their function. Superresolution microscopy can report on protein clustering and extract quantitative molecular information. Here, we evaluate the blinking kinetics of four photoactivatable fluorescent for single-molecule microscopy. We identified mEos3.2 mMaple3 to be suitable quantification through histogram analysis. designed synthetic genetic dimers as well fusion monomeric dimeric reference structures, demonstrate versatile use superresolution...
Abstract Live‐cell labeling, super‐resolution microscopy, single‐molecule applications, protein localization, or chemically induced assembly are emerging approaches, which require specific and very small interaction pairs. The minimal disturbance of function is essential to derive unbiased insights into cellular processes. Herein, we define a new class hexavalent N ‐nitrilotriacetic acid ( hexa NTA) chelators, displaying the highest affinity stability all NTA‐based pairs described so far....
RIG-I is a cytosolic receptor of viral RNA essential for the immune response to numerous viruses. Accordingly, must sensitively detect yet tolerate abundant self-RNA species. The basic binding cleft and an aromatic amino acid C-terminal domain(CTD) mediate high-affinity recognition 5'triphosphorylated 5'base-paired RNA(dsRNA). Here, we found that, while 5'unmodified hydroxyl(OH)-dsRNA demonstrated residual activation potential, 5'-monophosphate(5'p)-termini, present on most cellular RNAs,...
Extracellular signals drive the nucleation of NLRP3 inflammasome which leads to release cytokines and causes inflammatory events. Hence, has gained enormous momentum in biomedical basic research. The detailed mechanisms generation regulation remain be elucidated. Our study was directed toward design, convergent synthesis, initial biochemical evaluation activity-based probes addressing NLRP3. For this purpose, were assembled from a CRID3/MCC950-related NLRP3-binding unit, linker portion...
Label-free optical biosensors are an invaluable tool for molecular interaction analysis. Over the past 30 years, refractometric and, in particular, surface plasmon resonance have matured to
Abstract Cyclin-dependent kinase 7 (Cdk7) occupies a central position in cell-cycle and transcriptional regulation owing to its function as both CDK-activating (CAK) part of the general transcription factor TFIIH. Cdk7 forms an active complex upon association with Cyclin H Mat1, catalytic activity is regulated by two phosphorylations activation segment (T loop): canonical activating modification at T170 another S164. Here we report crystal structure fully activated human Cdk7/Cyclin H/Mat1...
Membrane receptor clustering is fundamental to cell-cell communication; however, the physiological function of in cell signaling remains enigmatic. Here, we developed a dynamic platform induce cluster formation neuropeptide Y2 hormone receptors (Y2R) situ by chelator nanotool. The multivalent interaction enabled exchange histidine-tagged Y2R within clusters. Fast enrichment clustered areas triggered ligand-independent as determined an increase cytosolic calcium and migration. Notably,...
Abstract Polyacrylamide gel electrophoresis (PAGE) and immunoblotting (Western blotting) are the most common methods in life science. In conjunction with these methods, polyhistidine-tag has proven to be a superb fusion tag for protein purification as well specific detection by immunoblotting, which led vast amount of commercially available antibodies. Nevertheless, antibody batch-to-batch variations nonspecific binding complicate laborious procedure. The interaction principle applied...
Abstract Small chemical/biological interaction pairs are at the forefront in tracing protein function and high signal‐to‐background ratios cellular pathways. However, optimal design of scaffold, linker, chelator head still deserve systematic investigation to achieve highest affinity kinetic stability for vitro especially applications. We report on a library N ‐nitrilotriacetic acid (NTA)‐based multivalent heads (MCHs) built linear, cyclic, dendritic scaffolds compare these with regard their...
Abstract Live‐cell labeling, super‐resolution microscopy, single‐molecule applications, protein localization, or chemically induced assembly are emerging approaches, which require specific and very small interaction pairs. The minimal disturbance of function is essential to derive unbiased insights into cellular processes. Herein, we define a new class hexavalent N ‐nitrilotriacetic acid ( hexa NTA) chelators, displaying the highest affinity stability all NTA‐based pairs described so far....
Summary Tripartite ATP-independent periplasmic (TRAP) transporters are widespread in bacteria and archaea provide important uptake routes for many metabolites 1–3 . They consist of three structural domains, a soluble substrate-binding protein (P-domain), two transmembrane domains (Q- M-domains) that form functional unit 4 While the structures P-domains well-known, an experimental structure any QM-domain has been elusive. HiSiaPQM is TRAP transporter monocarboxylate sialic acid, which plays...
TrisNTA-Chelatoren bestehen aus drei metallkomplexierenden N-Nitrilotriessigsäure(NTA)-Derivaten, die über eine Gerüststruktur verbunden sind. Gekoppelt an einen Fluorophor oder anderen Reporter können trisNTAs als Sonden für Kennzeichnung histidinmarkierter Proteine in lebenden Zellen dienen. R. Tampé et al. berichten ihrer Zuschrift auf S. 12575 große Affinitäts- und Stabilitätsunterschiede, durch lineare, dendritische cyclische Gerüste hervorgerufen werden, sie klären, welche...
SUMMARY RIG-I is a cytosolic receptor of viral RNA essential for the immune response to numerous viruses. Accordingly, must sensitively detect yet tolerate abundant self-RNA species. The basic binding cleft and an aromatic amino acid C-terminal domain(CTD) mediate high-affinity recognition 5’triphosphorylated 5’base-paired RNA(dsRNA). Here, we found that, while 5’unmodified hydroxyl(OH)-dsRNA demonstrated residual activation potential, 5’-monophosphate(5’p)-termini, present on most cellular...
Abstract Membrane receptors are central to cell-cell communication. Receptor clustering at the plasma membrane modulates physiological responses, and mesoscale receptor organization is critical for downstream signaling. Spatially restricted cluster formation of neuropeptide Y 2 hormone (Y R) was observed in vivo ; however, relevance this confinement not fully understood. Here, we controlled R situ by a chelator nanotool. Due multivalent interaction, dynamic exchange microscale confined...
Fluoreszenzsonden In ihrer Zuschrift auf S. 5722 berichten R. Tampé et al. über eine neue Klasse hexavalenter Chelatoren, welche die Auswahl an selektiven und hochaffinen Markierungspaaren vergrößert. Diese Sonden können Informationen dynamische zelluläre Prozesse liefern.