ArticleProceedings of the National Academy of Sciences of the United States of America2015
Buried ionizable networks are an ancient hallmark of G protein-coupled receptor activation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed.
- Article
- The Origins of GPCRs.International journal of molecular sciences · 2026Review
- Molecular and functional profiling of Gαi as an intracellular pH sensor.Nature communications · 2025Article
- VPS26 Moonlights as a β-Arrestin-like Adapter for a 7-Transmembrane RGS Protein inBiochemistry · 2024Article
- Stress pathway outputs are encoded by pH-dependent clustering of kinase components.Nature communications · 2024Article
- Accurately Predicting Protein pJournal of chemical theory and computation · 2023Article
- ALX/FPR2 Activation by Stereoisomers of D1 Resolvins Elucidating with Molecular Dynamics Simulation.The journal of physical chemistry. B · 2023Article
- Magic angle spinning NMR of G protein-coupled receptors.Progress in nuclear magnetic resonance spectroscopy · 2022Review
- Combinatorial phosphorylation modulates the structure and function of the G protein γ subunit in yeast.Science signaling · 2021Article
- Predictable cholesterol binding sites in GPCRs lack consensus motifs.Structure (London, England : 1993) · 2021Article
- One Year of SARS-CoV-2: How Much Has the Virus Changed?Biology · 2021Article
- Cancer and pH Dynamics: Transcriptional Regulation, Proteostasis, and the Need for New Molecular Tools.Cancers · 2020Review
- An acidic residue buried in the dimer interface of isocitrate dehydrogenase 1 (IDH1) helps regulate catalysis and pH sensitivity.The Biochemical journal · 2020Article
- The proton-sensing receptor ovarian cancer G-protein coupled receptor 1 (OGR1) in airway physiology and disease.Current opinion in pharmacology · 2020Review
- Common activation mechanism of class A GPCRs.eLife · 2019Article
- Regulation of ovarian cancer G protein-coupled receptor-1 expression and signaling.American journal of physiology. Lung cellular and molecular physiology · 2019Article
- Diverse GPCRs exhibit conserved water networks for stabilization and activation.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Mechanisms of signalling and biased agonism in G protein-coupled receptors.Nature reviews. Molecular cell biology · 2018Review
- Coupling between an electrostatic network and the ZnThe Journal of general physiology · 2018Article
- Coordinated regulation of intracellular pH by two glucose-sensing pathways in yeast.The Journal of biological chemistry · 2018Article
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2 authors.
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Abstract
Seven-transmembrane receptors (7TMRs) have evolved in prokaryotes and eukaryotes over hundreds of millions of years. Comparative structural analysis suggests that these receptors may share a remote evolutionary origin, despite their lack of sequence similarity. Here we used structure-based computations to compare 221 7TMRs from all domains of life. Unexpectedly, we discovered that these receptors contain spatially conserved networks of buried ionizable groups. In microbial 7TMRs these networks are used to pump ions across the cell membrane in response to light. In animal 7TMRs, which include light- and ligand-activated G protein-coupled receptors (GPCRs), homologous networks were found to be characteristic of activated receptor conformations. These networks are likely relevant to receptor function because they connect the ligand-binding pocket of the receptor to the nucleotide-binding pocket of the G protein. We propose that agonist and G protein binding facilitate the formation of these electrostatic networks and promote important structural rearrangements such as the displacement of transmembrane helix-6. We anticipate that robust classification of activated GPCR structures will aid the identification of ligands that target activated GPCR structural states.
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