A5078210924- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Chemical Synthesis and Analysis
- Monoclonal and Polyclonal Antibodies Research
- Protein Kinase Regulation and GTPase Signaling
- Biochemical Analysis and Sensing Techniques
- Enzyme Structure and Function
- Metabolism, Diabetes, and Cancer
- Glycosylation and Glycoproteins Research
- RNA and protein synthesis mechanisms
- Regulation of Appetite and Obesity
- Mass Spectrometry Techniques and Applications
- Computational Drug Discovery Methods
Australian Regenerative Medicine Institute
2023
Monash University
2023
VIB-VUB Center for Structural Biology
2020
Vrije Universiteit Brussel
2014-2020
Vlaams Instituut voor Biotechnologie
2014-2017
β-Arrestins (βarrs) interact with G protein-coupled receptors (GPCRs) to desensitize protein signaling, initiate signaling on their own, and mediate receptor endocytosis. Prior structural studies have revealed two unique conformations of GPCR-βarr complexes: the "tail" conformation, βarr primarily coupled phosphorylated GPCR C-terminal tail, "core" where, in addition is further engaged transmembrane core. However, relationship these distinct various functions βarrs unknown. Here, we created...
Abstract Ric-8A is a cytosolic Guanine Nucleotide exchange Factor (GEF) that activates heterotrimeric G protein alpha subunits (Gα) and serves as an essential Gα chaperone. Mechanisms by which catalyzes these activities, are stimulated Casein Kinase II phosphorylation, unknown. We report the structure of nanobody-stabilized complex nucleotide-free bound to phosphorylated at near atomic resolution cryo-electron microscopy X-ray crystallography. The mechanism GEF activity differs considerably...
G protein-coupled receptors (GPCRs) represent an important group of membrane proteins that play a central role in modern medicine. Unfortunately, conformational promiscuity hampers full therapeutic exploitation GPCRs, since the largest population receptor will adopt basal conformation, which subsequently challenges screens for agonist drug discovery programs. Herein, we describe set peptidomimetics able to mimic ability stabilizing active state β2 adrenergic (β2 AR) and dopamine 1 (D1R)....
GPCR–G-protein complexes are one of the most important components cell-signalling cascades. Extracellular signals sensed by membrane-associated G-protein-coupled receptors (GPCRs) and transduced via G proteins towards intracellular effector molecules. Structural studies these transient crucial to understand molecular details interactions. Although a nucleotide-free complex is stable, it not an ideal sample for crystallization owing intrinsic mobility Gαs α-helical domain (AHD). To stabilize...
Abstract The melanocortin receptor 4 (MC4R) belongs to the family of G-protein coupled receptors and is a key switch in leptin-melanocortin molecular axis that controls hunger satiety. Brain-produced hormones such as α-melanocyte-stimulating hormone (agonist) agouti-related peptide (inverse agonist) regulate communication MC4R but are promiscuous for subtypes induce wide array biological effects. Using conformation-selective ConfoBody, use active state-stabilized facilitated efficient de...
Ric-8A is a cytosolic Guanine Nucleotide exchange Factor (GEF) that activates heterotrimeric G protein alpha subunits (Gα) 1 . essential to life in multicellular eukaryotes by virtue of its chaperone activity required for Gα biogenesis and membrane localization 2, 3 adopts an armadillo (ARM)/HEAT repeat domain architecture structurally unrelated Protein-Coupled Receptors (GPCR) 4 Both GEF activities are stimulated Casein Kinase II phosphorylation 5 The mechanisms which catalyzes GDP release...
Abstract G protein‐coupled receptors (GPCRs) represent an important group of membrane proteins that play a central role in modern medicine. Unfortunately, conformational promiscuity hampers full therapeutic exploitation GPCRs, since the largest population receptor will adopt basal conformation, which subsequently challenges screens for agonist drug discovery programs. Herein, we describe set peptidomimetics able to mimic ability stabilizing active state β 2 adrenergic (β AR) and dopamine 1...