ArticleNature communications2017
Molecular mechanism of Gαi activation by non-GPCR proteins with a Gα-Binding and Activating motif.
Article in Nature communications, 2017. 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.
- Inhibitory probes for spatiotemporal analysis of GαNature chemical biology · 2026Article
- TrkB/mGluR5 cross-talk underlies a synaptic metaplasticity mechanism of ketamine.Science advances · 2026Article
- G protein regulation by RGS proteins in the pathophysiology of dilated cardiomyopathy.American journal of physiology. Heart and circulatory physiology · 2025Review
- Tackling Undruggable Targets with Designer Peptidomimetics and Synthetic Biologics.Chemical reviews · 2024Review
- Design, synthesis, and analysis of macrobicyclic peptides for targeting the Gαi protein.Journal of peptide science : an official publication of the European Peptide Society · 2024Article
- Heterotrimeric G protein signaling without GPCRs: The Gα-binding-and-activating (GBA) motif.The Journal of biological chemistry · 2024Review
- Synaptic plasticity via receptor tyrosine kinase/G-protein-coupled receptor crosstalk.Cell reports · 2024Article
- Bicyclic Peptide Library Screening for the Identification of Gαi Protein Modulators.Journal of medicinal chemistry · 2023Article
- Fine-tuning GPCR-mediated neuromodulation by biasing signaling through different G protein subunits.Molecular cell · 2023Article
- Small-molecule targeting of GPCR-independent noncanonical G-protein signaling in cancer.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Role of G-Proteins and GPCRs in Cardiovascular Pathologies.Bioengineering (Basel, Switzerland) · 2023Review
- RGS12 polarizes the GPSM2-GNAI complex to organize and elongate stereocilia in sensory hair cells.Science advances · 2022Article
- DAPLE orchestrates apical actomyosin assembly from junctional polarity complexes.The Journal of cell biology · 2022Article
- Targeting Gαi/s Proteins with Peptidyl Nucleotide Exchange Modulators.ACS chemical biology · 2022Article
- Building unconventional G protein-coupled receptors, one block at a time.Trends in pharmacological sciences · 2021Article
- Strategies towards Targeting Gαi/s Proteins: Scanning of Protein-Protein Interaction Sites To Overcome Inaccessibility.ChemMedChem · 2021Review
- Article
- Receptor tyrosine kinases activate heterotrimeric G proteins via phosphorylation within the interdomain cleft of Gαi.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Optogenetic activation of heterotrimeric G-proteins by LOV2GIVe, a rationally engineered modular protein.eLife · 2020Article
- Do All Roads Lead to Rome in G-Protein Activation?Trends in biochemical sciences · 2020Review
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
Heterotrimeric G proteins are quintessential signalling switches activated by nucleotide exchange on Gα. Although activation is predominantly carried out by G-protein-coupled receptors (GPCRs), non-receptor guanine-nucleotide exchange factors (GEFs) have emerged as critical signalling molecules and therapeutic targets. Here we characterize the molecular mechanism of G-protein activation by a family of non-receptor GEFs containing a Gα-binding and -activating (GBA) motif. We combine NMR spectroscopy, computational modelling and biochemistry to map changes in Gα caused by binding of GBA proteins with residue-level resolution. We find that the GBA motif binds to the SwitchII/α3 cleft of Gα and induces changes in the G-1/P-loop and G-2 boxes (involved in phosphate binding), but not in the G-4/G-5 boxes (guanine binding). Our findings reveal that G-protein-binding and activation mechanisms are fundamentally different between GBA proteins and GPCRs, and that GEF-mediated perturbation of nucleotide phosphate binding is sufficient for Gα activation.
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