ArticleNature structural & molecular biology2021
GPCR activation mechanisms across classes and macro/microscales.
Article in Nature structural & molecular biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 176 papers.
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Who cites it
176 citing papers in PubMed.
- Structural insights into the ligand modulation of MRGPRX4 conformational plasticity.Cell discovery · 2026Article
- Atomic, structural and molecular insights into GPCR ligand binding and signalling.Nature reviews. Molecular cell biology · 2026Review
- A co-evolved peptide-GPCR system senses host entry to drive fungal infection.Nature communications · 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
- Host membrane cholesterol constrains constitutive signaling of the oncogenic KSHV GPCR ORF74.bioRxiv : the preprint server for biology · 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
- Article
- Agonist Binding Reshapes the Kinetic Landscape and Allosteric Communication of APLNR Toward Activation-Competent States.International journal of molecular sciences · 2026Article
- Article
- 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
- De novo design of miniproteins targeting GPCRs.Nature · 2026Article
- Next-generation chemogenetic inhibition using a brain-permeant non-prescription agent.Signal transduction and targeted therapy · 2026Article
- Molecular architecture of OXGR1 reveals an evolutionary conserved mechanisms for metabolite surveillance.The EMBO journal · 2026Article
- Mechanistic and therapeutic insights into class A GPCR dimers in neuropsychiatric disorders.npj drug discovery · 2026Review
- Targeting frizzleds with small-molecule compounds-back to square one or light at the end of the tunnel?The Journal of biological chemistry · 2026Review
- Structure-based screening and a conformational biosensor identify a GPR183 inverse agonist and an activation switch.Nature communications · 2026Article
- Improving AlphaFold2 Performance in Virtual Screens Targeting GPCRs by Enhancing Binding-Site Conformational Sampling.Journal of chemical information and modeling · 2026Article
116 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Two-thirds of human hormones and one-third of clinical drugs activate ~350 G-protein-coupled receptors (GPCR) belonging to four classes: A, B1, C and F. Whereas a model of activation has been described for class A, very little is known about the activation of the other classes, which differ by being activated by endogenous ligands bound mainly or entirely extracellularly. Here we show that, although they use the same structural scaffold and share several 'helix macroswitches', the GPCR classes differ in their 'residue microswitch' positions and contacts. We present molecular mechanistic maps of activation for each GPCR class and methods for contact analysis applicable for any functional determinants. This provides a superfamily residue-level rationale for conformational selection and allosteric communication by ligands and G proteins, laying the foundation for receptor-function studies and drugs with the desired modality.
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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.