ArticleScience (New York, N.Y.)2020
Molecular mechanism of biased signaling in a prototypical G protein-coupled receptor.
Article in Science (New York, N.Y.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 141 papers.
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Who cites it
141 citing papers in PubMed, 239 citations in OpenAlex.
- Molecular Determinants of G Protein Subtype-Specific Coupling to the Angiotensin II Type 1 Receptor.bioRxiv : the preprint server for biology · 2026Article
- Configurational diversity of metabotropic glutamate receptor complexes with beta-arrestins.Nature communications · 2026Article
- Steric control of signaling bias in the immunometabolic receptor GPR84.Nature communications · 2026Article
- Arrestins as programmable integrators of GPCR signaling: structural microstates, spatiotemporal logic, and therapeutic control.Cell discovery · 2026Review
- Discovery of Biased Dual-Agonists of Glucagon-Like Peptide 1 and Glucagon Receptors through Mutation of a Conserved Aspartate.ACS medicinal chemistry letters · 2026Article
- Targeting tumor-associated G-protein coupled receptors: beyond single-axis inhibition toward multidimensional regulation.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Structural Basis of GPCR-Biased Modulation.Handbook of experimental pharmacology · 2026Review
- Structural and Computational Insights into the Angiotensin II Type 1 Receptor: Advances in Antagonist Design and Implications for Hypertension Therapy (2020-2024).Biomolecules · 2025Review
- Structural insights into the G-protein subtype selectivity revealed by human sphingosine-1-phosphate receptor 3-GProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Conformational Heterogeneity Underlying Divergent Signaling in Class A G Protein-Coupled Receptors.ACS pharmacology & translational science · 2025Review
- Structural and dynamic insights into the biased signaling mechanism of the human kappa opioid receptor.Nature communications · 2025Article
- Unbiased Enhanced Sampling in Molecular Dynamics via Simultaneously Accelerating Diffusion in Multiple Low-Dimensional Collective Variable Spaces.Journal of chemical theory and computation · 2025Article
- Biased signalingActa pharmaceutica Sinica. B · 2025Review
- Mechanistic insights into the versatile stoichiometry and biased signaling of the apelin receptor-arrestin complex.Nature communications · 2025Article
- G protein-coupled receptors: pivotal hubs in gastric cancer malignancy-from multidimensional crosstalk to precision therapeutics.Journal of translational medicine · 2025Review
- Structural insights into GPCR signaling activated by peptide ligands: from molecular mechanism to therapeutic application.Experimental & molecular medicine · 2025Review
- Article
- Multiple intramolecular triggers converge to preferential G protein coupling in the CBNature communications · 2025Article
- ProGuide: a flexible framework for modeling global conformational rearrangements in proteins using DEER-derived distance restraints.bioRxiv : the preprint server for biology · 2025Article
- Gating Mechanism for Biased Agonism at Angiotensin II Type 1 Receptors.Molecules (Basel, Switzerland) · 2025Article
81 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Biased signaling, in which different ligands that bind to the same G protein-coupled receptor preferentially trigger distinct signaling pathways, holds great promise for the design of safer and more effective drugs. Its structural mechanism remains unclear, however, hampering efforts to design drugs with desired signaling profiles. Here, we use extensive atomic-level molecular dynamics simulations to determine how arrestin bias and G protein bias arise at the angiotensin II type 1 receptor. The receptor adopts two major signaling conformations, one of which couples almost exclusively to arrestin, whereas the other also couples effectively to a G protein. A long-range allosteric network allows ligands in the extracellular binding pocket to favor either of the two intracellular conformations. Guided by this computationally determined mechanism, we designed ligands with desired signaling profiles.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.