A5046786993- Receptor Mechanisms and Signaling
- Monoclonal and Polyclonal Antibodies Research
- Photoreceptor and optogenetics research
- Chemical Synthesis and Analysis
- Lipid Membrane Structure and Behavior
- Retinal Development and Disorders
- Click Chemistry and Applications
- Neuropeptides and Animal Physiology
- Chemokine receptors and signaling
- Protein Structure and Dynamics
- Neuroscience and Neuropharmacology Research
- Mass Spectrometry Techniques and Applications
- Immune Cell Function and Interaction
- HIV Research and Treatment
- Glycosylation and Glycoproteins Research
- Peptidase Inhibition and Analysis
- Dendrimers and Hyperbranched Polymers
- Cell Adhesion Molecules Research
- Advanced biosensing and bioanalysis techniques
- Ocular Oncology and Treatments
- T-cell and B-cell Immunology
- Synthesis and properties of polymers
- Soybean genetics and cultivation
- Climate Change and Health Impacts
- Infection Control and Ventilation
Rockefeller University
2016-2025
Novartis (Switzerland)
2013-2023
Novartis Institutes for BioMedical Research
2013-2023
Ludwig-Maximilians-Universität München
1999-2019
Center for Integrated Protein Science Munich
2015
Biolog (United States)
2014
Bielefeld University
2006-2011
University of Zurich
2002-2009
MRC Laboratory of Molecular Biology
2008
Biotechnology Institute
2007
Many integral membrane proteins assemble to form oligomeric structures in biological membranes. In particular, seven-transmembrane helical G protein-coupled receptors (GPCRs) appear self-assemble constitutively membranes, but the mechanism and physiological role of this assembly are unknown. We developed employed coarse-grain molecular dynamics (CGMD) models investigate basis how physicochemical properties phospholipid bilayer affect self-assembly visual rhodopsin, a prototypical GPCR. The...
The G protein-coupled receptor (GPCR) rhodopsin self-assembles into supramolecular structures in native bilayers, but the structural determinants of oligomerization are not known. We carried out multiple self-assembly coarse-grained molecular dynamics (CGMD) simulations model membranes containing up to 64 molecules visual over time scales reaching 100 μs. show strong preferential interaction modes between receptors. Two primary receptor-receptor interactions consistent with umbrella...
G protein-coupled receptors (GPCRs) are ubiquitous heptahelical transmembrane proteins involved in a wide variety of signaling pathways. The work described here on application unnatural amino acid mutagenesis to two GPCRs, the chemokine receptor CCR5 (a major co-receptor for human immunodeficiency virus) and rhodopsin (the visual photoreceptor), adds new dimension studies GPCRs. We incorporated acids p-acetyl-L-phenylalanine (Acp) p-benzoyl-L-phenylalanine (Bzp) into at high efficiency...
Significance Targeting WNT (Wingless-type)/β-catenin signaling has emerged as an attractive novel therapeutic approach to the treatment of bone diseases. We previously identified LRP4 (low-density lipoprotein receptor-related protein 4) a facilitator action antagonist SOST/sclerostin in vitro. Here, we generated bone-specific Lrp4 -deficient mouse lines and anti-LRP4 antibodies selectively disrupting sclerostin function. Using these genetic pharmacological tools, demonstrate that disruption...
Polyunsaturated phospholipids are known to be important with regard the biological functions of essential fatty acids, for example, involving neural tissues such as brain and retina. Here we have employed two complementary structural methods study polyunsaturated bilayer lipids, viz. deuterium (2H) NMR spectroscopy molecular dynamics (MD) computer simulations. Our research constitutes one first applications all-atom MD simulations lipids containing docosahexaenoic acid (DHA; 22:6...
We developed a general cell-based photocrosslinking approach to investigate the binding interfaces necessary for formation of G protein-coupled receptor (GPCR) signaling complexes. The two photoactivatable unnatural amino acids p-benzoyl-L-phenylalanine and p-azido-L-phenylalanine were incorporated by amber codon suppression technology into CXC chemokine 4 (CXCR4). then probed ligand-binding site HIV-1 coreceptor blocker, T140, using fluorescein-labeled T140 analogue. Among eight acid...
Receptor activity-modifying proteins (RAMPs) have been shown to modulate the functions of several G protein-coupled receptors (GPCRs), but potential direct interactions among three known RAMPs and hundreds GPCRs never investigated. Focusing mainly on secretin-like family GPCRs, we engineered epitope-tagged RAMPs, developed a multiplexed suspension bead array (SBA) immunoassay detect GPCR-RAMP complexes from detergent-solubilized lysates. Using 64 antibodies raised against native 4 targeting...
Crystal structures of engineered human β2-adrenergic receptors (ARs) in complex with an inverse agonist ligand, carazolol, provide three-dimensional snapshots the disposition seven transmembrane helices and ligand-binding site important G protein-coupled receptor (GPCR). As expected, β2-AR shares substantial structural similarities rhodopsin, dim-light photoreceptor rod cell. However, although carazolol 11-cis-retinylidene moiety rhodopsin are situated same general binding pocket, second...
G protein-coupled receptors form dimers and higher-order oligomers in membranes, but the precise mode of receptor–receptor interaction remains unknown. To probe intradimeric proximity helix 8 (H8), we conducted chemical cross-linking endogenous cysteines rhodopsin disk membranes. We identified a Cys316–Cys316 cross-link using partial proteolysis liquid chromatography with mass spectrometry. These results show that symmetric dimer interface mediated by H1 H8 contacts is present native
Abstract Despite the well-established role of human serotonin transporter (hSERT) in treatment depression, molecular details antidepressant drug binding are still not fully understood. Here we utilize amber codon suppression a membrane-bound protein to encode photocrosslinking unnatural amino acids (UAAs) into 75 different positions hSERT. UAAs incorporated with high specificity, and functionally active transporters have similar transport properties pharmacological profiles compared...
Novel methods are required for site-specific, quantitative fluorescent labeling of G-protein-coupled receptors (GPCRs) and other difficult-to-express membrane proteins. Ideally, probes should perturb the native structure function as little possible. We evaluated bioorthogonal reactions to label genetically encoded p-acetyl-L-phenylalanine (AcF) or p-azido-L-phenylalanine (azF) residues in heterologously expressed mammalian cells. found that keto-selective reagents were not truly...
In mice, the transfer of CD172a(+) (SIRP-α) dendritic cells (DCs) elicits T cell-driven colitis, whereas treatment with CD47-Fc protein, a CD172a-binding agent, confers protection. The aim this study was to elucidate nature and functional properties human DCs in chronic intestinal inflammation. Here, we show that CD172a(+)CD11c(+) accumulate mesenteric lymph nodes (mLNs) inflamed mucosa patients Crohn's disease (CD). These are distinct from resident may coexpress markers typically associated...