Daniel Hilger
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View article: Unraveling allosteric signaling of G protein-coupled receptors (GPCRs) by single-molecule fluorescence
Unraveling allosteric signaling of G protein-coupled receptors (GPCRs) by single-molecule fluorescence Open
G protein-coupled receptors (GPCRs) are the largest and most functionally diverse family of membrane receptors in eukaryotes. They play central roles in numerous physiological processes and are implicated in a wide range of diseases, makin…
View article: Cryo-EM structure of a cell-free synthesized full-length human β1-adrenergic receptor in complex with Gs
Cryo-EM structure of a cell-free synthesized full-length human β1-adrenergic receptor in complex with Gs Open
The third intracellular loop (ICL3) of the β1-adrenergic receptor (β1AR) plays a critical role in regulating G protein coupling, yet the structural basis has remained unclear due to truncations of ICL3 in all available structures of the β1…
View article: Ligand-dependent G protein dynamics underlying opioid signaling efficacy
Ligand-dependent G protein dynamics underlying opioid signaling efficacy Open
Activation of heterotrimeric G proteins by G protein-coupled receptors (GPCRs) requires large-scale opening of the Gα α-helical domain (AHD) to expose the nucleotide-binding site and facilitate GDP-GTP exchange. While orthosteric ligands a…
View article: GPR3 ligands discovered through combined virtual and conformational biosensor-based screening
GPR3 ligands discovered through combined virtual and conformational biosensor-based screening Open
GPR3 belongs to the protein superfamily of G protein-coupled receptors (GPCRs) and plays a central role in both benign and malignant physiological processes, such as energy expenditure in adipocytes and Alzheimer’s disease pathology, respe…
View article: Cryo-EM structure of a cell-free synthesized full-length human β1-adrenergic receptor in complex with G<sub>s</sub>
Cryo-EM structure of a cell-free synthesized full-length human β1-adrenergic receptor in complex with G<sub>s</sub> Open
SUMMARY The third intracellular loop (ICL3) of the β1-adrenergic receptor (β1AR) plays a critical role in regulating G protein coupling, yet the structural basis has remained unclear due to truncations of ICL3 in all available structures o…
View article: Cryo-EM structure of cell-free synthesized human histamine 2 receptor/Gs complex in nanodisc environment
Cryo-EM structure of cell-free synthesized human histamine 2 receptor/Gs complex in nanodisc environment Open
Here we describe the cryo-electron microscopy structure of the human histamine 2 receptor (H 2 R) in an active conformation with bound histamine and in complex with G s heterotrimeric protein at an overall resolution of 3.4 Å. The complex …
View article: A virtual library of small molecules mimicking dipeptides
A virtual library of small molecules mimicking dipeptides Open
Virtual combinatorial libraries are prevalent in drug discovery due to improvements in the prediction of synthetic reactions that can be performed. This has gone hand in hand with the development of virtual screening capabilities to effect…
View article: Structural response of G protein binding to the cyclodepsipeptide inhibitor FR900359 probed by NMR spectroscopy
Structural response of G protein binding to the cyclodepsipeptide inhibitor FR900359 probed by NMR spectroscopy Open
The selective G q inhibitor FR900359 was probed by NMR spectroscopy bound to the membrane-anchored G q heterotrimer, revealing its mode of membrane interaction, protein binding and allosteric protein response.
View article: Editorial: New approaches for the discovery of GPCR ligands
Editorial: New approaches for the discovery of GPCR ligands Open
EDITORIAL article Front. Endocrinol., 21 August 2023Sec. Cellular Endocrinology Volume 14 - 2023 | https://doi.org/10.3389/fendo.2023.1272700
View article: Cryo-EM structure of cell-free synthesized human histamine H<sub>2</sub>receptor coupled to heterotrimeric G<sub>s</sub>protein in lipid nanodisc environment
Cryo-EM structure of cell-free synthesized human histamine H<sub>2</sub>receptor coupled to heterotrimeric G<sub>s</sub>protein in lipid nanodisc environment Open
Here we describe the cryo-electron microscopy structure of the human histamine 2 receptor (H 2 R) in an active conformation with bound histamine and in complex with G s heterotrimeric protein at an overall resolution of 3.4 Å. The complex …
View article: Numerical Analysis and Reduced‐Order Modeling of Plastic Profile Extrusion Processes
Numerical Analysis and Reduced‐Order Modeling of Plastic Profile Extrusion Processes Open
We present the data‐driven standardized non‐intrusive reduced‐order modeling strategy, sniROM, applied in context of plastics profile extrusion. After a brief introduction to the process and the governing physics, we give a short overview …
View article: Time-resolved cryo-EM of G protein activation by a GPCR
Time-resolved cryo-EM of G protein activation by a GPCR Open
Summary G protein-coupled receptors (GPCRs) activate heterotrimeric G proteins by stimulating the exchange of guanine nucleotide in the Gα subunit. To visualize this mechanism, we developed a time-resolved cryo-EM approach that examines th…
View article: Negative allosteric modulation of the glucagon receptor by RAMP2
Negative allosteric modulation of the glucagon receptor by RAMP2 Open
Receptor activity-modifying proteins (RAMPs) modulate the activity of many Family B GPCRs. We show that RAMP2 directly interacts with the glucagon receptor (GCGR), a Family B GPCR responsible for blood sugar homeostasis, and broadly inhibi…
View article: Decision Support for the Optimization of Continuous Processes using Digital Shadows
Decision Support for the Optimization of Continuous Processes using Digital Shadows Open
Decision support systems can provide real-time process information and correlations, which in turn assists process experts in making decisions and thus further increase productivity. This also applies to well-established and already highly…
View article: A Data-driven Reduced Order Modeling Approach Applied In Context Of Numerical Analysis And Optimization Of Plastic Profile Extrusion
A Data-driven Reduced Order Modeling Approach Applied In Context Of Numerical Analysis And Optimization Of Plastic Profile Extrusion Open
In course of this work, we examine the process of plastic profile extrusion, where a polymer melt is shaped inside the so-called extrusion die and fixed in its shape by solidification in the downstream calibration unit. More precise, we fo…
View article: Negative allosteric modulation of the glucagon receptor by RAMP2
Negative allosteric modulation of the glucagon receptor by RAMP2 Open
Receptor activity-modifying proteins (RAMPs) modulate the activity of many Family B heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs). The glucagon receptor (GCGR), a Family B GPCR responsible for main…
View article: Investigation of Physics-Informed Deep Learning for the Prediction of Parametric, Three-Dimensional Flow Based on Boundary Data
Investigation of Physics-Informed Deep Learning for the Prediction of Parametric, Three-Dimensional Flow Based on Boundary Data Open
The placement of temperature sensitive and safety-critical components is crucial in the automotive industry. It is therefore inevitable, even at the design stage of new vehicles that these components are assessed for potential safety issue…
View article: Structures of active melanocortin-4 receptor−Gs-protein complexes with NDP-α-MSH and setmelanotide
Structures of active melanocortin-4 receptor−Gs-protein complexes with NDP-α-MSH and setmelanotide Open
SUMMARY The melanocortin-4 receptor (MC4R), a hypothalamic master regulator of energy homeostasis and appetite, is a G-protein coupled receptor and a prime target for the treatment of obesity. Here, we present cryo-electron microscopy stru…
View article: The role of structural dynamics in GPCR‐mediated signaling
The role of structural dynamics in GPCR‐mediated signaling Open
G protein‐coupled receptors (GPCRs) play critical roles in the regulation of human physiology in response to a wide array of different extracellular stimuli and thus represent one of the largest groups of therapeutic drug targets. Recent a…
View article: Viewing rare conformations of the β <sub>2</sub> adrenergic receptor with pressure-resolved DEER spectroscopy
Viewing rare conformations of the β <sub>2</sub> adrenergic receptor with pressure-resolved DEER spectroscopy Open
Significance The molecular origin of basal activity in G protein coupled receptors and its suppression by inverse agonists are poorly understood. Here we employ pressure-resolved DEER spectroscopy to explore the structural origin of basal …
View article: Structural insights into differences in G protein activation by family A and family B GPCRs
Structural insights into differences in G protein activation by family A and family B GPCRs Open
Revealing family differences In response to low blood glucose concentrations, both the glucagon receptor (GCGR)—a family B G protein–coupled receptor (GPCR)—and the β 2 adrenergic receptor (β 2 AR)—a family A GPCR—are activated and act thr…
View article: Time-resolved Conformational Analysis during GPCR-Gs Coupling
Time-resolved Conformational Analysis during GPCR-Gs Coupling Open
Protein-protein interactions and conformational changes of a signaling protein are major mechanisms of cellular signal transduction. To understand the precise signaling mechanism, studies have investigated the structural mechanism of signa…