A5072113688- Proteoglycans and glycosaminoglycans research
- Collagen: Extraction and Characterization
- Silk-based biomaterials and applications
- Toxoplasma gondii Research Studies
- DNA Repair Mechanisms
- Glycosylation and Glycoproteins Research
- Protein Kinase Regulation and GTPase Signaling
- Chemical Synthesis and Analysis
- CRISPR and Genetic Engineering
- Supramolecular Self-Assembly in Materials
- PI3K/AKT/mTOR signaling in cancer
- Cytomegalovirus and herpesvirus research
- Genomics and Chromatin Dynamics
- Cell Adhesion Molecules Research
- 14-3-3 protein interactions
- Herpesvirus Infections and Treatments
- Melanoma and MAPK Pathways
- Diatoms and Algae Research
- Medicinal plant effects and applications
- Mosquito-borne diseases and control
- Cancer Research and Treatments
- Cell death mechanisms and regulation
- Modular Robots and Swarm Intelligence
- Cancer-related Molecular Pathways
- Galectins and Cancer Biology
The Francis Crick Institute
2017-2025
Helmholtz-Zentrum Hereon
2011-2016
University of Potsdam
2011-2016
Berlin-Brandenburger Centrum für Regenerative Therapien
2015
Homologous recombination (HR) is an essential DNA double-strand break (DSB) repair mechanism, which frequently inactivated in cancer. During HR, RAD51 forms nucleoprotein filaments on RPA-coated, resected and catalyzes strand invasion into homologous duplex DNA. How displaces RPA assembles long HR-proficient remains uncertain. Here, we employed single-molecule imaging to investigate the mechanism of nematode RAD-51 filament growth presence BRC-2 (BRCA2) paralogs, RFS-1/RIP-1. nucleates...
N-myristoylation is a ubiquitous class of protein lipidation across eukaryotes and N-myristoyl transferase (NMT) has been proposed as an attractive drug target in several pathogens. Myristoylation often primes for subsequent palmitoylation stable membrane attachment, however, growing evidence suggests additional regulatory roles myristoylation on proteins. Here we describe the myristoylated proteome Toxoplasma gondii using chemoproteomic methods show that small-molecule NMT inhibitor...
Peptidylarginine deiminase IV (PADI4, PAD4) deregulation promotes the development of autoimmunity, cancer, atherosclerosis and age-related tissue fibrosis. PADI4 additionally mediates immune responses cellular reprogramming, although full extent its physiological roles is unexplored. Despite detailed molecular knowledge activation in vitro, we lack understanding regulation within cells, largely due to a appropriate systems tools. Here, develop apply set potent selective modulators. Using...
Mimicking the binding epitopes of protein-protein interactions by using small peptides is important for generating modular biomimetic systems. A strategy described design such bioactive without accessible structural data targeted interaction, and effect incorporating adhesion in complex biomaterial systems demonstrated. The highly repetitive structure decorin was analyzed to identify that are representative inner outer surface, it shown only based on surface bind collagen. peptide with...
Abstract Peptidylarginine deiminase IV (PADI4) deregulation promotes the development of autoimmunity, cancer, atherosclerosis and age-related tissue fibrosis. Genetic or pharmacological PADI4 inhibition is therapeutically efficacious in mice, but no clinically relevant inhibitors currently exist. additionally mediates immune responses cellular reprogramming, although full extent its physiological roles unexplored. Despite detailed molecular knowledge activation vitro , we lack understanding...
CDC7 is an essential Ser/Thr kinase that acts upon the replicative helicase throughout S phase of cell cycle and activated by DBF4. Here, we present crystal structures a highly active human CDC7-DBF4 construct. The reveal zinc-finger domain at end insert 2 pins activation loop to motif M DBF4 C lobe CDC7. These interactions lead ordering substrate-binding platform full opening site. In co-crystal structure with mimic MCM2 Ser40 phosphorylation target, invariant residues Arg373 Arg380 engage...
Abstract Sister-chromatid cohesion is established by Eco1-mediated acetylation on two conserved tandem lysines in the cohesin Smc3 subunit. However, molecular basis of Eco1 substrate recognition and not fully understood. Here, we discover rationalize specificity using mass spectrometry coupled with in-vitro assays crystallography. Our structures X. laevis Eco2 (xEco2) bound to its primary secondary substrates demonstrate plasticity substrate-binding site, which confers concerted...
Abstract The Aurora B abscission checkpoint delays cytokinesis until resolution of DNA trapped in the cleavage furrow. This process involves PKCε phosphorylation S227. Assessing if this PKCε-Aurora module provides a more widely exploited genome-protective control for cell cycle, we show at S227 by also occurs during mitosis. Expression S227A phenocopies inhibition by-passing delay and anaphase entry that is associated with non-disjunction catenation sister chromatids. Implementation...
P110α is a member of the phosphoinositide 3-kinase (PI3K) enzyme family that functions downstream RAS. RAS proteins contribute to activation p110α by interacting directly with its binding domain (RBD), resulting in promotion many cellular such as cell growth, proliferation and survival. Previous work from our lab has highlighted importance p110α/RAS interaction tumour initiation growth. Here we report discovery characterisation cyclic peptide inhibitor (cyclo-CRVLIR) interacts p110α-RBD...
ABSTRACT Homologous recombination (HR) is an essential DNA double-strand break (DSBs) repair mechanism frequently inactivated in cancer. During HR, RAD51 forms nucleoprotein filaments on RPA-coated resected and catalyses strand invasion into homologous duplex DNA. How displaces RPA assembles long HR-proficient remains uncertain. Here, we employ single-molecule imaging to investigate the of nematode RAD-51 filament growth presence BRC-2 (BRCA2) paralogs, RFS-1/RIP-1. nucleates DNA, while...
Abstract Das Nachbilden der Bindungsepitope von Protein‐Protein‐Wechselwirkungen mithilfe kleiner Peptide ist wichtig bei Entwicklung modularer biomimetischer Systeme. Hier beschreiben wir eine Strategie zum Design solcher bioaktiver Peptide, ohne dass Strukturdaten des Proteinkomplexes benötigt werden, und weisen den Effekt Inkorporierung Adhäsionssequenzen in komplexen Biomaterialsystemen nach. Dazu wurde die hochrepetitive Struktur Decorin analysiert. Für dessen innere sowie äußere...
Abstract A peptide showing propensity for the adoption of β‐sheet conformation was synthesized in order to develop a defined molecular building block as part toolbox development polymer networks based on supramolecular interactions. The by microwave‐assisted solid phase synthesis and purification performed Reversed Phase‐High Performance Liquid Chromatography (RP‐HPLC), from which purity higher than 95 mol‐% obtained. calculated mass confirmed Matrix Assisted Laser Desorption Ionization‐Time...
Abstract N -myristoylation is a ubiquitous class of protein lipidation across eukaryotes and -myristoyl transferase has been proposed as an attractive drug target in several pathogens. Functionally the myristate often primes for subsequent palmitoylation stable membrane attachment, however, growing evidence also suggests additional regulatory roles myristoylation on proteins. Here we describe first global chemoproteomic screening Toxoplasma gondii . Through quantitative mass spectrometry...
Abstract p110α is a member of the phosphoinositide 3-kinase (PI3K) enzyme family that functions downstream RAS. RAS proteins contribute to activation by interacting directly with its binding domain (RBD), resulting in promotion many cellular such as cell growth, proliferation and survival. Previous work from our lab has highlighted importance p110α/RAS interaction tumour initiation growth. Here we report discovery characterisation cyclic peptide inhibitor (cyclo-CRVLIR) interacts p110α-RBD...