A5003122127- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Monoclonal and Polyclonal Antibodies Research
- Hypothalamic control of reproductive hormones
- Cancer-related gene regulation
- Hippo pathway signaling and YAP/TAZ
- Chemical Synthesis and Analysis
- Protein Kinase Regulation and GTPase Signaling
- Estrogen and related hormone effects
- Phosphodiesterase function and regulation
- Skin Protection and Aging
- Biosimilars and Bioanalytical Methods
- Protein Structure and Dynamics
- Wnt/β-catenin signaling in development and cancer
- Advanced Proteomics Techniques and Applications
- Computational Drug Discovery Methods
- Glycosylation and Glycoproteins Research
- Enzyme Structure and Function
- Ovarian function and disorders
- Bioactive Compounds and Antitumor Agents
- Tuberculosis Research and Epidemiology
- Heat shock proteins research
- Apelin-related biomedical research
- Immune Response and Inflammation
- Biological Activity of Diterpenoids and Biflavonoids
Bayer (Germany)
2023-2025
Leibniz-Forschungsinstitut für Molekulare Pharmakologie
2010-2021
Freie Universität Berlin
2019-2021
Leibniz Association
2012-2016
Leibniz Institute for Neurobiology
2012-2015
Max Planck Institute for Molecular Genetics
2009
Pseudomonas aeruginosa rapidly adapts to altered conditions by quorum sensing (QS), a communication system that it uses collectively modify its behavior through the production, release, and detection of signaling molecules. QS molecules can also be sensed hosts, although respective receptors pathways are poorly understood. We describe pattern regulation in host aryl hydrocarbon receptor (AhR) is critically dependent on qualitative quantitative P. quorum. bind AhR distinctly modulate...
Abstract Background G protein-coupled receptors (GPCRs) transduce a wide variety of extracellular signals to within the cell and therefore have key role in regulating activity physiological function. GPCR malfunction is responsible for range diseases including cancer, diabetes hyperthyroidism large proportion drugs on market target these receptors. The three dimensional structure GPCRs important elucidating molecular mechanisms underlying performing structure-based drug design. Although...
The hormone thyrotropin (TSH) and its receptor (TSHR) are crucial for the growth function of thyroid gland. TSHR is evolutionary linked with receptors follitropin (FSHR) lutropin/choriogonadotropin (LHR) their sequences structures similar. extracellular region contains more than 350 amino acids binds antibodies. Several important questions related to functions mechanisms still not comprehensively understood. One major reason these open lack any structural information about segment that...
A good fit: Interactions between A-kinase anchoring proteins (AKAPs) and protein kinase (PKA) play key roles in a plethora of physiologically relevant processes whose dysregulation causes or is associated with diseases such as heart failure. Terpyridines have been developed α-helix mimetics for the inhibition interactions are first biologically active, nonpeptidic compounds that block AKAP binding site PKA.
The human lutropin (hLH)/choriogonadotropin (hCG) receptor (LHCGR) can be activated by binding two slightly different gonadotropic glycoprotein hormones, choriogonadotropin (CG) - secreted the placenta, and (LH) produced pituitary. They induce signaling profiles at LHCGR. This cannot explained to receptor's leucine-rich-repeat domain (LRRD), as this is similar for hormones. We therefore speculate that there are previously unknown differences in hormone/receptor interaction extracellular...
Over the last few decades pharmaceutical industry has generated a vast corpus of knowledge on safety and efficacy drugs. Much this information is contained in toxicology reports, which summarise results animal studies designed to analyse effects tested compound, including unintended pharmacological toxic effects, known as treatment-related findings. Despite potential knowledge, fact that most relevant only available unstructured text with variable degrees digitisation hampered its systematic...
N-terminal signal peptides mediate the interaction of native proteins with translocon complex endoplasmic reticulum membrane and are cleaved off during early protein biogenesis. The corticotropin-releasing factor receptor type 2a (CRF2(a)R) possesses an pseudo peptide, which represents a so far unique domain within large family G protein-coupled receptors (GPCRs). In contrast to conventional peptide remains uncleaved consequently forms hydrophobic extension at N terminus receptor. functional...
G-protein coupled receptors (GPCRs) are key players in signal transduction and therefore a large proportion of pharmaceutical drugs target these receptors. Structural data GPCRs sparse yet important for elucidating the molecular basis GPCR-related diseases performing structure-based drug design. To ameliorate this problem, GPCR-SSFE 2.0 (http://www.ssfa-7tmr.de/ssfe2/), an intuitive web server dedicated to providing three-dimensional Class A GPCR homology models has been developed. The...
A-kinase anchoring proteins (AKAPs) interact with the dimerization/docking (D/D) domains of regulatory subunits ubiquitous protein kinase A (PKA). AKAPs tether PKA to defined cellular compartments establishing distinct pools increase specificity signalling. Here, we elucidated structure an extended PKA-binding domain AKAP18β bound D/D RIIα PKA. We identified three hydrophilic anchor points in outside core domain, which mediate contacts domain. Such are conserved within that bind RII derived...
Abstract As a first host barrier, the skin is constantly exposed to environmental insults that perturb its integrity. Tight regulation of homeostasis largely controlled by aryl hydrocarbon receptor (AhR). Here, we demonstrate Henna and major pigment, naphthoquinone Lawsone activate AhR, both in vitro vivo . In human keratinocytes epidermis equivalents, exposure enhances production late epidermal proteins, impacts keratinocyte differentiation proliferation, regulates inflammation. To...
Transmembrane helices (TMHs) 5 and 6 are known to be important for signal transduction by G-protein-coupled receptors (GPCRs). Our aim was characterize the interface between TMH5 TMH6 of thyrotropin receptor (TSHR) gain molecular insights into aspects regulation. A proline at position 5.50 is highly conserved in family GPCRs causes a twist helix structure. Mutation TSHR-specific alanine (Ala-593⁵·⁵⁰) this resulted 20-fold reduction cell surface expression. This indicates that TSHR might have...
The SSFA-GPHR (Sequence-Structure-Function-Analysis of Glycoprotein Hormone Receptors) database provides a comprehensive set mutation data for the glycoprotein hormone receptors (covering lutropin, FSH, and TSH receptors). Moreover, it platform comparison investigation these homologous helps in understanding protein malfunctions associated with several diseases. Besides extending (> 1100 mutations), has been completely redesigned novel features analysis tools have added to web site. These...
The first version of a glycoprotein hormone receptor (GPHR) information resource was designed to link functional with structural GPHR information, in order support sequence-structure-function analysis the LH, FSH, and TSH receptors (http://ssfa-gphr.de). However, on binding- signaling-sensitive extracellular fragment (∼100 residues), hinge region, had been lacking. A new FSHR crystal structure hormone-bound domain has recently solved. comprises leucine-rich repeat most parts region. We have...
Evaluating the functional relevance of naturally occurring gene variants usually requires experimental testing or is even impossible because lack appropriate assays. Here we have analyzed whether comparative sequence data from orthologs are suitable to predict mutations in a model protein, G-proteincoupled receptor for ADP (P2Y12). The effect every possible substitution at each amino acid position within portion P2Y12 (1254 mutants) was individually determined. Sequence analysis >70...
The large TSH-bound ectodomain of the thyrotropin receptor (TSHR) activates transmembrane domain (TMD) indirectly via an internal agonist (IA). ectodomain/TMD interface consists a converging helix, Cys-Cys-bridge-linked IA, and extracellular loops (ECL). To investigate intramolecular course molecular activation, especially details indirect we narrowed down allosteric inhibition sites negative modulator (NAM) by mutagenesis, homology modeling, competition studies with positive (PAM). From...
The collection, description and molecular analysis of naturally occurring (pathogenic) mutations are important for understanding the functional mechanisms malfunctions biological units such as proteins. Numerous databases collate a huge amount data or descriptions mutations, but tools to analyse effects genetic variations yet poorly provided. goal this work was therefore develop translational web-application that facilitates interactive linkage structural which helps improve our basis gain-...
<b><i>Introduction:</i></b> G protein-coupled receptor (GPCR) mutations are implicated in many diseases. Most inactivating cause misfolding and prevent trafficking to the plasma membrane. Pharmacological chaperones can “rescue” cell surface expression of such mutants, presumably by stabilising correct folding nascent protein. <b><i>Objective:</i></b> Here we examine scope intracellularly retained luteinising hormone (LHR) mutants that be...
(1) The human luteinizing hormone (LH)/chorionic gonadotropin (hCG) receptor (LHCGR) discriminates its two ligands and differs from the murine (Lhr) in amino acid residues potentially involved qualitative discerning of LH hCG. latter is absent rodents. aim study to identify LHCGR hCG/LH discrimination. (2) Eight cDNAs were developed, carrying “murinizing” mutations on aminoacidic assumed interact specifically with LH, hCG, or both. HEK293 cells expressing a mutant wild type treated hCG...
With growing amount of experimental data, the number known protein structures also increases continuously. Classification helps to understand relationships between structure and function. The main classification methods based on secondary are SCOP, CATH TOPS, which all classify under different aspects, therefore can lead results. We developed a mathematically unique representation topologies at higher abstraction level providing new aspects enabling for fast search through data. Protein...