Search Results
521 items found for "Jespers W"
- Endosomal parathyroid hormone receptor signaling
This is the case for the parathyroid hormone (PTH) type 1 receptor (PTHR), which engages on sustained
- Nanobodies as Probes and Modulators of Cardiovascular G Protein-Coupled Receptors
Here, we review how nanobodies have been adopted to elucidate the structure, pharmacology, and signaling We also discuss how advancing technologies to discover nanobodies with tailored specificities may expand
- High hedgehog signaling is transduced by a multikinase-dependent switch controlling the...
G-protein-coupled receptor (GPCR) Smoothened (SMO) is a key transducer of the hedgehog (HH) morphogen, which Here, we examine how HH controls SMO subcellular localization and activity in a polarized epithelium using the Drosophila wing imaginal disc as a model. We provide evidence that HH promotes the stabilization of SMO by switching its fate after endocytosis
- Structural perspectives on the mechanism of signal activation, ligand selectivity and allosteric...
Thus, we need to know much more about the structures of receptor-ligand complexes at high resolution.
- Mechanistic basis of GPCR activation explored by ensemble refinement of crystallographic structures
Recent advances in X-ray crystallography and cryo-EM have resulted in a wealth of GPCR structures that
- Structure of the vasopressin hormone-V2 receptor-β-arrestin1 ternary complex
Recent structural studies shed light on the molecular mechanisms involved in GPCR-arrestin coupling, but whether Here, we report the cryo-electron microscopy active structure of the wild-type arginine-vasopressin V2
- ADGRL3 genomic variation implicated in neurogenesis and ADHD links functional effects to the...
Protein-Coupled Receptor L3 (ADGRL3) gene are associated with increased susceptibility to developing ADHD worldwide Using several bioinformatics tools to evaluate the impact of mutations, we found that nsSNPs rs35106420 rs734644, previously reported to be associated and in linkage with ADHD in disparate populations from the world of bioinformatics tools showed that functional mutations in the ADGLR3 gene disrupt the standard and wild
- Allosteric modulation of GPCRs: From structural insights to in silico drug discovery
While traditional drug discovery programs have focused on the development of ligands targeting the binding In this review, we provide a systematic analysis of the currently available GPCR structures in complex In addition, we summarize current strategies for the identification of allosteric sites as well as ligand-based
- Dual loss of regulator of G protein signaling 2 and 5 exacerbates ventricular myocyte arrhythmias...
Whether RGS2 and 5 redundantly control G protein signaling to maintain cardiovascular homeostasis is Here we examined how the dual absence of RGS2 and 5 (Rgs2/5 dbKO) affects blood pressure and cardiac
- Case Report of a Juvenile Patient with Autism Spectrum Disorder with a Novel Combination of Copy...
Spectrum Disorder with a Novel Combination of Copy Number Variants in ADGRL3 (LPHN3) and Two Pseudogenes "We Using array-based comparative genomic hybridization (array-CGH), we identified two CNVs, both triplex
- Identification of A2BAR as a potential target in colorectal cancer using novel fluorescent GPCR...
novel fluorescent GPCR ligands "G-protein coupled receptors (GPCRs) have been largely targeted in a wide Here, using colorectal cancer (CRC) as a model, we explored the gene expression of a panel of GPCRs in We selected the adenosine receptor 2B (A2BAR), specifically expressed in cancer cell lines compared with As well, fluorescent ligands were effective at monitoring real-time A2BAR receptor labeling using live-imaging Finally, we validated A2BAR as a potential pharmacological tool in CRC, using selective antagonists,
- Increased Anxiety-like Behaviors in Adgra1-/- Male But Not Female Mice are Attributable to...
We found that Adgra1 is highly and exclusively expressed in the brain, suggesting that Adgra1 may be To this end, we comprehensively analyzed the potential role of ADGRA1 in the neurobehaviors of mice by comparing Adgra1-/- and their wild-type (wt) littermates. Finally, we found that PI3K/AKT/GSK-3β and MEK/ERK in amygdalae of Adgra1-deficient male mice were aberrantly activated when compared to wt male mice.
- Intermolecular Interactions in G Protein-Coupled Receptor Allosteric Sites at the Membrane Interface
In this work, we analyze interactions in the allosteric sites of the PAR2, C5aR1, and GCGR receptors We show that besides classical hydrogen bonds, weak polar interactions such as O-HC, O-Br, and long-range The availability of polar atoms for interactions in such cavities can be assessed by water molecules Although ligand-lipid interactions are weak, lipid tails play a role in ligand binding pose stability library enriched by weak donor groups for ligand search in such sites."
- Structural basis of adhesion GPCR GPR110 activation by stalk peptide and G-proteins coupling
Here, we report the cryo-electron microscopy structures of GPR110 (ADGRF1), a member of aGPCR, in complex This is also where Gq/Gs bind the receptor through both hydrophobic and polar interaction, while Gi/G12 We further provide physiological evidence of GPR110 activation via stalk peptide.
- Endogenous ligand recognition and structural transition of a human PTH receptor
two ligands have distinct signaling and physiological properties: PTH evokes prolonged Gs activation, whereas Here, we report cryoelectron microscopic structures of six forms of the human PTH1R-Gs complex in the
- Discovery and In Vivo Evaluation of ACT-660602: A Potent and Selective Antagonist of the Chemokine..
Starting from a high-throughput screening hit, we describe the iterative optimization of a chemical series significantly reduced recruitment of the CXCR3+ CD8+ T cell in the bronchoalveolar lavage compartment when
- Structural view of G protein-coupled receptor signaling in the retinal rod outer segment
We summarize recent discoveries that have advanced our understanding of rod outer segment (ROS) morphology We have combined recently published cryo-electron tomography (cryo-ET) data on the ROS with structural knowledge on individual proteins to define the precise spatial limitations under which phototransduction guanylate cyclases (GCs) in maintaining the spacing between ROS discs, suggesting a plausible mechanism by which
- GPCR Agonist-to-Antagonist Conversion: Enabling the Design of Nucleoside Functional Switches for...
Herein, we demonstrate that a thiophene modification at the C8 position in the common adenine scaffold We synthesized and characterized a novel A2AAR antagonist, 2 (LJ-4517), with Ki = 18.3 nM. X-ray crystallographic structures of 2 in complex with two thermostabilized A2AAR constructs were solved In contrast to A2AAR agonists, which simultaneously interact with both Ser2777.42 and His2787.43, 2 only transiently contacts His2787.43, which can be direct or water-mediated.
- Novel Therapies for Cardiometabolic Disease: Recent Findings in Studies with Hormone...
One successful strategy is the so-called metabolic surgery whose beneficial effects are beyond dietary restrictions and weight loss. , glucagon, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) which animal models and ongoing clinical trials using these unimolecular dual and triagonists are included which These therapeutic strategies could greatly impact the treatment of CVD with unprecedented benefits which
- N-terminal alterations turn the gut hormone GLP-2 into an antagonist with gradual loss of GLP-2 ...
Searching for antagonist activity, we performed systematic N-terminal truncations of human GLP-2(1-33 Experimental approach: COS-7 cells were transfected with the human GLP-2R and assessed for cAMP accumulation To examine selectivity, COS-7 cells expressing human GLP-1 or GIP receptors were assessed for cAMP accumulation
- Adrenal G Protein-Coupled Receptors and the Failing Heart: A Long-distance, Yet Intimate Affair
characterized by the reduction in cardiac function and still remains the disease with the highest mortality worldwide This is why sympatholytic treatments (such as β-blockers) and renin-angiotensin system inhibitors or mineralocorticoid receptor antagonists, which block the effects of angiotensin II (AngII) and aldosterone In this review, we discuss important aspects of adrenal GPCR signaling and regulation, as they pertain
- Glucagon receptor-mediated regulation of gluconeogenic gene transcription is endocytosis-dependent..
We tested if this is true for the glucagon receptor (GCGR), which mediates physiological regulation of We show that epitope-tagged GCGRs undergo clathrin- and dynamin-dependent endocytosis in HEK293 and Huh -7-Lunet cells after activation by glucagon within 5 min and transit via EEA1-marked endosomes shown We further show that endocytosis potentiates cytoplasmic cAMP elevation produced by GCGR activation and We verify endocytosis-dependent induction of PCK1 expression by endogenous GCGRs in primary hepatocytes
- GB83, an Agonist of PAR2 with a Unique Mechanism of Action Distinct from Trypsin and PAR2-AP
In the present study, we found that GB83, initially identified as a PAR2 antagonist, is a bona fide agonist recovery of the localization and function of PAR2 was significantly delayed after stimulation by GB83, which may be the reason why GB83 is recognized as an antagonist of PAR2.
- The complicated lives of GPCRs in cardiac fibroblasts
October 2022 "The role of different G protein-coupled receptors (GPCRs) in the cardiovascular system is well In the former, stimulation of Gs-coupled receptors leads to increases in contractility, whereas stimulation Here, we will focus on the relatively less well-studied effects of GPCRs in cardiac fibroblasts, focusing We discuss how such events may be distinct depending on where the GPCRs and their associated signaling Finally, we explore what such connections between the cell surface and nuclear GPCR signaling might mean
- Differences across sexes on head-twitch behavior and 5-HT2A receptor signaling in C57BL/6J mice
This class of psychoactive substances, which includes lysergic acid diethylamide (LSD), psilocybin, mescaline Here we tested the effects of DOI on head-twitch behavior (HTR) - a mouse behavioral proxy of human psychedelic the pharmacokinetic properties of DOI differed among sexes - brain and plasma concentrations of DOI were
- The Adhesion GPCR VLGR1/ADGRV1 Regulates the Ca2+ Homeostasis at Mitochondria-Associated ER Membrane
associated with the human Usher syndrome (USH), the most common form of inherited deaf-blindness as well interactome of VLGR1, molecules are enriched that are associated with both the ER and mitochondria, as well We confirmed the interaction of VLGR1 with key proteins of MAMs by pull-down assays in vitro complemented
- Lysosomal GPCR-like protein LYCHOS signals cholesterol sufficiency to mTORC1
Through bioinformatic analysis of lysosomal proteomes, we identified lysosomal cholesterol signaling
- Production of human A2AAR in lipid nanodiscs for 19F-NMR and single-molecule fluorescence...
October 2022 "We describe production of the human A2A adenosine receptor (A2AAR), a class A G protein-coupled We explain in detail steps shared between the two sample preparation strategies, including expression For complete details on the use and execution of this protocol, please refer to Wei et al. (2022) and