A5008671847- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Neuroendocrine regulation and behavior
- Spectroscopy and Quantum Chemical Studies
- Advanced Electron Microscopy Techniques and Applications
- Lipid Membrane Structure and Behavior
- Protein Structure and Dynamics
- Circadian rhythm and melatonin
- Electron and X-Ray Spectroscopy Techniques
- Chemical Synthesis and Analysis
- Microstructure and mechanical properties
- Mass Spectrometry Techniques and Applications
- Hypothalamic control of reproductive hormones
University of Zurich
2020-2022
Neurotensin receptor 1 (NTSR1) and related G protein-coupled receptors of the ghrelin family are clinically unexploited, several mechanistic aspects their activation inactivation have remained unclear. Enabled by a new crystallization design, we present five structures: apo-state NTSR1 as well complexes with nonpeptide inverse agonists SR48692 SR142948A, partial agonist RTI-3a, novel full SRI-9829, providing structural rationales on how ligands modulate NTSR1. The favor large extracellular...
Neuropeptide-bound NK 1 R:G protein complex structures explain mechanisms ranging from insurmountable antagonism to activation.
Abstract α-adrenergic receptors (αARs) are G protein-coupled that regulate vital functions of the cardiovascular and nervous systems. The therapeutic potential αARs, however, is largely unexploited hampered by scarcity subtype-selective ligands. Moreover, several aminergic drugs either show off-target binding to αARs or fail interact with desired subtype. Here, we report crystal structure human α 1B AR bound inverse agonist (+)-cyclazosin, enabled fusion a DARPin crystallization chaperone....
The small cyclic neuropeptide hormone oxytocin (OT) and its cognate receptor play a central role in the regulation of social behaviour sexual reproduction. Here we report single-particle cryo-electron microscopy structure active (OTR) complex with ligand oxytocin. Our provides high-resolution insights into OT binding mode, OTR activation mechanism as well subtype specificity within oxytocin/vasopressin family.
The presence of preferred orientations in single particle analysis (SPA) by cryo-Electron Microscopy (cryoEM) is currently one the hurdles preventing many structural analyses from yielding high-resolution structures. Although existence mostly related to grid preparation, this technical note, we show that some image processing algorithms used for angular assignment and three-dimensional (3D) reconstruction are more robust than others these detrimental conditions. We exemplify argument with...
Sample preparation for NMR studies of G protein-coupled receptors faces special requirements: Proteins need to be stable prolonged measurements at elevated temperatures, they should ideally uniformly labeled with the isotopes 13C, 15N, and all carbon-bound protons replaced by deuterons. In addition, certain experiments require protonated methyl groups in presence a perdeuterated background. All these requirements are most easily satisfied when using Escherichia coli as expression host. Here...
Abstract The small cyclic neuropeptide hormone oxytocin (OT) and its cognate receptor play a central role in the regulation of social behaviour sexual reproduction. Here we report single-particle cryo-electron microscopy structure active (OTR) complex with ligand oxytocin. Our provides high-resolution insights into OT binding mode, OTR activation mechanism as well subtype specificity within oxytocin/vasopressin family.