A5041564152- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Computational Drug Discovery Methods
- Monoclonal and Polyclonal Antibodies Research
- Protein Kinase Regulation and GTPase Signaling
McGill University
2019-2023
McGill University Health Centre
2022
G protein–coupled receptors engage both proteins and β-arrestins, their coupling can be biased by ligands mutations. Here, to resolve structural elements mechanisms underlying effector the angiotensin II (AngII) type 1 receptor (AT1R), we combined alanine scanning mutagenesis of entire sequence with pharmacological profiling Gα q β-arrestin engagement mutant molecular dynamics simulations. We showed that AT1R involved a large number residues spread across receptor, whereas fewer regions...
The angiotensin II (AngII) type 1 receptor (AT1R) is a member of the G protein–coupled (GPCR) family and binds β-arrestins (β-arrs), which regulate AT1R signaling trafficking. These processes can be biased by different ligands or mutations in AGTR1 gene. As for many GPCRs, exact details AT1R–β-arr interactions driven AngII β-arr–biased remain largely unknown. Here, we used amber-suppression technology to site-specifically introduce unnatural amino acid (UAA) p-azido-l-phenylalanine (azF)...
Promiscuous G protein-coupled receptors (GPCRs) engage multiple Gα subtypes with different efficacies to propagate signals in cells. A mechanistic understanding of selectivity by GPCRs is critical for therapeutic design, since signaling can be restrained ligand-receptor complexes preferentially specific proteins. However, details GPCR are unresolved. Here, we investigated cognate protein using the prototypical promiscuous Gαq/11 and Gα12/13 coupling receptors, angiotensin II type I receptor...