ArticleProceedings of the National Academy of Sciences of the United States of America2019
Structural basis for GPCR-independent activation of heterotrimeric Gi proteins.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 25 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 50 citations in OpenAlex.
- β-arrestin recruitment facilitates a direct association with G proteins.Nature communications · 2026Article
- Going Rogue: Mechanisms, Regulation, and Roles of Mutationally Activated GMolecular pharmacology · 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
- Bicyclic Peptide Library Screening for the Identification of Gαi Protein Modulators.Journal of medicinal chemistry · 2023Article
- Article
- 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
- A circuit for secretion-coupled cellular autonomy in multicellular eukaryotic cells.Molecular systems biology · 2023Article
- Regulation of DNA damage response by trimeric G-proteins.iScience · 2023Article
- Design principles of improving the dose-response alignment in coupled GTPase switches.NPJ systems biology and applications · 2023Article
- Targeting Gαi/s Proteins with Peptidyl Nucleotide Exchange Modulators.ACS chemical biology · 2022Article
- Delineating the activation mechanism and conformational landscape of a class B G protein-coupled receptor glucagon receptor.Computational and structural biotechnology journal · 2022Article
- Article
- 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
- 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
- Regulating cellular cyclic adenosine monophosphate: "Sources," "sinks," and now, "tunable valves".Wiley interdisciplinary reviews. Systems biology and medicine · 2020Review
- GIV/Girdin and Exo70 Collaboratively Regulate the Mammalian Polarized Exocytic Machinery.iScience · 2020Article
- GIV•Kindlin Interaction Is Required for Kindlin-Mediated Integrin Recognition and Activation.iScience · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Heterotrimeric G proteins are key molecular switches that control cell behavior. The canonical activation of G proteins by agonist-occupied G protein-coupled receptors (GPCRs) has recently been elucidated from the structural perspective. In contrast, the structural basis for GPCR-independent G protein activation by a novel family of guanine-nucleotide exchange modulators (GEMs) remains unknown. Here, we present a 2.0-Å crystal structure of Gαi in complex with the GEM motif of GIV/Girdin. Nucleotide exchange assays, molecular dynamics simulations, and hydrogen-deuterium exchange experiments demonstrate that GEM binding to the conformational switch II causes structural changes that allosterically propagate to the hydrophobic core of the Gαi GTPase domain. Rearrangement of the hydrophobic core appears to be a common mechanism by which GPCRs and GEMs activate G proteins, although with different efficiency. Atomic-level insights presented here will aid structure-based efforts to selectively target the noncanonical 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.