ArticleeLife2019
Common activation mechanism of class A GPCRs.
Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 358 papers.
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Who cites it
358 citing papers in PubMed, 646 citations in OpenAlex.
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- Development of a clinically viable MRGPRX4 inverse agonist for cholestatic itch treatment.Nature chemical biology · 2026Article
- Structural basis of stepwise G protein activation by the viral chemokine receptor US28.bioRxiv : the preprint server for biology · 2026Article
- Mechanism of GPR84 allosteric modulation at a helix 8-proximate site.Science advances · 2026Article
- A Minimalist Model for Navigating Conformational Landscape Uncovers the Activation Mechanism of βACS physical chemistry Au · 2026Article
- Uncoupling of the allosteric signalling network in the βNature communications · 2026Article
- Structure-based design of subtype-selective psychedelic analogs.Nature communications · 2026Article
- Residue Interaction Network Reveals Allosteric Pathways Linking Orthosteric and Intracellular Sites in Class A GPCRs.Journal of chemical information and modeling · 2026Article
- Structural basis of active state coupling of metabotropic glutamate receptor 8 to beta-arrestins.Nature communications · 2026Article
- Steric control of signaling bias in the immunometabolic receptor GPR84.Nature communications · 2026Article
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- Atypical signaling, ligand recognition and selective agonist discovery of complement receptor C5aR2.Cell research · 2026Article
- The structure of the dopamine DScience advances · 2026Article
- From Structure to Dynamics: Activation Mechanism of the G Protein-Coupled Bile Acid Receptor 1‑GACS omega · 2026Article
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- Structural insights on the ligand selectivity of the mouse trace amine-associated receptor TAAR7e.iScience · 2026Article
- DeorphaNN: Virtual screening of GPCR peptide agonists using AlphaFold-predicted active-state complexes and deep learning embeddings.Molecular cell · 2026Article
298 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
Abstract
Class A G-protein-coupled receptors (GPCRs) influence virtually every aspect of human physiology. Understanding receptor activation mechanism is critical for discovering novel therapeutics since about one-third of all marketed drugs target members of this family. GPCR activation is an allosteric process that couples agonist binding to G-protein recruitment, with the hallmark outward movement of transmembrane helix 6 (TM6). However, what leads to TM6 movement and the key residue level changes of this movement remain less well understood. Here, we report a framework to quantify conformational changes. By analyzing the conformational changes in 234 structures from 45 class A GPCRs, we discovered a common GPCR activation pathway comprising of 34 residue pairs and 35 residues. The pathway unifies previous findings into a common activation mechanism and strings together the scattered key motifs such as CWxP, DRY, Na
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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.