Peptide modifications differentially alter G protein-coupled receptor internalization and signaling bias. [PDF]
Angew Chem Int Ed Engl, 2014 Although G protein-coupled receptors (GPCRs) are targeted by more clinically used drugs than any other type of protein, their ligand development is particularly challenging.
Mäde V +9 more
europepmc +2 more sources
Allostery: allosteric networks and allosteric signaling bias
Quarterly Reviews of BiophysicsAbstract Allosteric communication is established by networks through which strain energy generated at the allosteric site by an allosteric event, such as ligand binding, can propagate to the functional site. Exerted on multiple molecules in the cell, it can wield a biased function. Here, we discuss
Ruth Nussinov +2 more
openaire +3 more sources
Molecular mechanism of biased signaling at the kappa opioid receptor
Nature Communications, 2023 Biased signaling in κ-opiod receptors (KOR) offer an attractive strategy for pain management. Here the authors identify determinants of KOR signaling bias using structural methods in combination with molecular dynamics simulations.
Amal El Daibani +13 more
doaj +2 more sources
Signaling bias of the protease-activated receptor-1 is dictated by distinct GRK5 and β-arrestin-2 determinants [PDF]
Cell ReportsSummary: G protein-coupled receptors (GPCRs) exhibit signaling bias or preferential activation of heterotrimeric G proteins versus GPCR kinase (GRK)-mediated β-arrestin signaling.
Monica L. Gonzalez Ramirez +7 more
doaj +2 more sources
Cannabinoid CB 1 and CB 2 Receptor Signaling and Bias
Cannabis and Cannabinoid Research, 2017 An agonist that acts through a single receptor can activate numerous signaling pathways. Recent studies have suggested that different ligands can differentially activate these pathways by stabilizing a limited range of receptor conformations, which in ...
Michelle Glass, Mark Connor
exaly +2 more sources
Modeling of Bias for the Analysis of Receptor Signaling in Biochemical Systems
Biochemistry, 2012 Ligand bias is a recently introduced concept in the receptor signaling field that underlies innovative strategies for targeted drug design. Ligands, as a consequence of conformational selectivity, produce signaling bias in which some downstream biochemical pathways are favored over others, and this contributes to variability in physiological ...
Sean Peterson
exaly +3 more sources
A GLP-1 analogue optimized for cAMP-biased signaling improves weight loss in obese mice
Molecular MetabolismObjective: Glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) agonism is foundational to modern obesity pharmacotherapies. These compounds were engineered for maximal G protein alpha(s) (Gsα) signaling potency and downstream cAMP production. However, this
Jonathan D. Douros +21 more
doaj +2 more sources
Phylogenetic Signal and Bias in Paleontology [PDF]
Systematic Biology, 2021 AbstractAn unprecedented amount of evidence now illuminates the phylogeny of living mammals and birds on the Tree of Life. We use this tree to measure the phylogenetic value of data typically used in paleontology (bones and teeth) from six data sets derived from five published studies.
Asher, Robert, Smith, Martin
openaire +3 more sources
GPCR Binding and JNK3 Activation by Arrestin-3 Have Different Structural Requirements
Cells, 2023 Arrestins bind active phosphorylated G protein-coupled receptors (GPCRs). Among the four mammalian subtypes, only arrestin-3 facilitates the activation of JNK3 in cells.
Chen Zheng +5 more
doaj +1 more source
The Role of ICL1 and H8 in Class B1 GPCRs; Implications for Receptor Activation
Frontiers in Endocrinology, 2022 The first intracellular loop (ICL1) of G protein-coupled receptors (GPCRs) has received little attention, although there is evidence that, with the 8th helix (H8), it is involved in early conformational changes following receptor activation as well as ...
Ian Winfield +10 more
doaj +1 more source