ArticleMolecular cell2021
A universal allosteric mechanism for G protein activation.
Article in Molecular cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 70 citations in OpenAlex.
- Protein Frustration Reveals Orthosteric and Allosteric Active Sites in GPCR:G Protein Complexes.Journal of chemical information and modeling · 2026Article
- Prevalence, distribution, and mechanisms of genetic dominance in the yeast mating pathway.Genetics · 2026Article
- Conserved residues in the Gα interface show subtype specificity in Gβγ coupling.The Journal of biological chemistry · 2026Article
- G-protein regulatory network governs receptor internalization dynamics.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
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- The role of the tryptophan-rich allosteric network and sodium egress in GPCR activation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Conserved Residues in the Gα interface show subtype specificity in Gβγ coupling.bioRxiv : the preprint server for biology · 2026Article
- Deciphering a mechanistic basis for the pathological effect of the GNAO1 E246K variant in neurodevelopmental disorder.BBA advances · 2026Article
- Regulation of MRGPRX2-mediated mast cell function by competence-stimulating peptide 1 and pro-adrenomedullin peptide.Frontiers in immunology · 2026Article
- Review
- Prevalence, distribution, and mechanisms of genetic dominance in the yeast mating pathway.bioRxiv : the preprint server for biology · 2025Article
- Dominant Gα mutations in human disease: unifying mechanisms and treatment strategies.EMBO molecular medicine · 2025Review
- Molecular and functional profiling of Gαi as an intracellular pH sensor.Nature communications · 2025Article
- Influence of expression and purification protocols on Gα biochemical activity: kinetics of plant and mammalian G protein cycles.Frontiers in molecular biosciences · 2025Article
- Essential strategies for the detection of constitutive and ligand-dependent Gi-directed activity of 7TM receptors using bioluminescence resonance energy transfer.bioRxiv : the preprint server for biology · 2024Article
- Germline mutations in a G protein identify signaling cross-talk in T cells.Science (New York, N.Y.) · 2024Article
- Stabilization of interdomain closure by a G protein inhibitor.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Get Ready to Sharpen Your Tools: A Short Guide to Heterotrimeric G Protein Activity Biosensors.Molecular pharmacology · 2024Review
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
G proteins play a central role in signal transduction and pharmacology. Signaling is initiated by cell-surface receptors, which promote guanosine triphosphate (GTP) binding and dissociation of Gα from the Gβγ subunits. Structural studies have revealed the molecular basis of subunit association with receptors, RGS proteins, and downstream effectors. In contrast, the mechanism of subunit dissociation is poorly understood. We use cell signaling assays, molecular dynamics (MD) simulations, and biochemistry and structural analyses to identify a conserved network of amino acids that dictates subunit release. In the presence of the terminal phosphate of GTP, a glycine forms a polar network with an arginine and glutamate, putting torsional strain on the subunit binding interface. This "G-R-E motif" secures GTP and, through an allosteric link, discharges the Gβγ dimer. Replacement of network residues prevents subunit dissociation regardless of agonist or GTP binding. These findings reveal the molecular basis of the final committed step of G protein activation.
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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.