The ability of structurally distinct ligands to "bias" G protein-coupled receptor signaling affords the opportunity to tailor efficacy to suit specific therapeutic needs. Furness et al. demonstrate that ligand structure controls not only which effectors are activated, but also the way they are activated and the kinetics of downstream signaling.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.cell.2016.10.006 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Structural insights into the engagement of lysophosphatidic acid receptor 1 with different G proteins.
J Struct Biol
December 2024
Advanced Research Institute, Institute of Science Tokyo, 1-5-45 Yushima Bunkyo-ku 113-8510, Tokyo, Japan. Electronic address:
Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are bioactive lysophospholipids derived from cell membranes that activate the endothelial differentiation gene family of G protein-coupled receptors. Activation of these receptors triggers multiple downstream signaling cascades through G proteins such as Gi/o, Gq/11, and G12/13. Therefore, LPA and S1P mediate several physiological processes, including cytoskeletal dynamics, neurite retraction, cell migration, cell proliferation, and intracellular ion fluxes.
View Article and Find Full Text PDFAn in silico framework to visualize how cancer-associated mutations influence structural plasticity of the chemokine receptor CCR3.
Protein Sci
January 2025
Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas, USA.
G protein Coupled Receptors (GPCRs) are the largest family of cell surface receptors in humans. Somatic mutations in GPCRs are implicated in cancer progression and metastasis, but mechanisms are poorly understood. Emerging evidence implicates perturbation of intra-receptor activation pathway motifs whereby extracellular signals are transmitted intracellularly.
View Article and Find Full Text PDFNon-canonical signaling initiated by hormone-responsive G protein-coupled receptors from subcellular compartments.
Pharmacol Ther
December 2024
Fang Zongxi Center for Marine EvoDevo, MoE Key Laboratory of Marine Genetics and Breeding, College of Marine Life Sciences, Ocean University of China, Qingdao 266003, China; Insititute of Evolution & Marine Biodiversity, Ocean University of China, Qingdao 266003, China.. Electronic address:
G protein-coupled receptors (GPCRs), the largest family of membrane receptors in the mammalian genomes, regulate almost all known physiological processes by transducing numerous extracellular stimuli including almost two-thirds of endogenous hormones and neurotransmitters. The traditional view held that GPCR signaling occurs exclusively at the cell surface, where the receptors bind with the ligands and undergo conformational changes to recruit and activate heterotrimeric G proteins. However, with the application of advanced biochemical and biophysical techniques, this conventional model is challenged by the elucidation of spatiotemporal GPCR activation with the evidence that receptors can signal from subcellular compartments to exhibit various molecular and cellular responses with physiological and pathophysiological relevance.
View Article and Find Full Text PDFAbsence of Functional Autoantibodies Targeting Angiotensin II Type 1 Receptor (ATR) and Endothelin-1 Type A Receptor (ETR) in Circulation and Purified IgG from Patients with Systemic Sclerosis.
Arthritis Rheumatol
December 2024
Department of Rheumatology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
Objective: Systemic sclerosis (SSc) is a rare but severe autoimmune disease characterized by immune dysregulation, fibrosis, and vasculopathy. While previous studies have highlighted the presence of functional autoantibodies targeting the angiotensin II type 1 receptor (ATR) and endothelin-1 type A receptor (ETR), leading to autoantibody-mediated receptor stimulation and subsequent activation of endothelial cells (ECs), a comprehensive understanding of the direct interaction between these autoantibodies and their receptors is currently lacking. Moreover, existing data confirming the presence of these autoantibodies in SSc often rely on similar methodologies and assays.
View Article and Find Full Text PDFBiased signaling in GPCRs: Structural insights and implications for drug development.
Pharmacol Ther
December 2024
Cancer Center and Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, United States. Electronic address:
G protein-coupled receptors (GPCRs) are the largest family of cell surface receptors in humans, playing a crucial role in regulating diverse cellular processes and serving as primary drug targets. Traditional drug design has primarily focused on ligands that uniformly activate or inhibit GPCRs. However, the concept of biased agonism-where ligands selectively stabilize distinct receptor conformations, leading to unique signaling outcomes-has introduced a paradigm shift in therapeutic development.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!