ArticleMolecular biology and evolution2016
Evolutionary Conservation of a GPCR-Independent Mechanism of Trimeric G Protein Activation.
Article in Molecular biology and evolution, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 38 citations in OpenAlex.
- Unveiling the Genomic Symphony: Identification Cultivar-Specific Genes and Enhanced Insights on Sweet Sorghum Genomes Through Comprehensive superTranscriptomic Analysis.Journal of molecular evolution · 2024Article
- Heterotrimeric G protein signaling without GPCRs: The Gα-binding-and-activating (GBA) motif.The Journal of biological chemistry · 2024Review
- FEZF2 and AIRE1: An Evolutionary Trade-off in the Elimination of Auto-reactive T Cells in the Thymus.Journal of molecular evolution · 2024Article
- Synaptic plasticity via receptor tyrosine kinase/G-protein-coupled receptor crosstalk.Cell reports · 2024Article
- DAPLE orchestrates apical actomyosin assembly from junctional polarity complexes.The Journal of cell biology · 2022Article
- Identification and evolutionary analysis of papillomavirus sequences in New World monkeys (genera Sapajus and Alouatta) from Argentina.Archives of virology · 2022Article
- Nakazawaea odontotermitis f.a., sp. nov., a novel yeast isolated from the gut of Odontotermes horni in India.Archives of microbiology · 2022Article
- Article
- 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
- Ric-8A, a GEF, and a Chaperone for G Protein α-Subunits: Evidence for the Two-Faced Interface.BioEssays : news and reviews in molecular, cellular and developmental biology · 2020Article
- DAPLE protein inhibits nucleotide exchange on GαThe Journal of biological chemistry · 2020Article
- GPCR-independent activation of G proteins promotes apical cell constriction in vivo.The Journal of cell biology · 2019Article
- G Proteins and GPCRs in C. elegans Development: A Story of Mutual Infidelity.Journal of developmental biology · 2018Review
- A biochemical and genetic discovery pipeline identifies PLCδ4b as a nonreceptor activator of heterotrimeric G-proteins.The Journal of biological chemistry · 2018Article
- When Heterotrimeric G Proteins Are Not Activated by G Protein-Coupled Receptors: Structural Insights and Evolutionary Conservation.Biochemistry · 2018Article
- Specific inhibition of GPCR-independent G protein signaling by a rationally engineered protein.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Molecular mechanism of Gαi activation by non-GPCR proteins with a Gα-Binding and Activating motif.Nature communications · 2017Article
- The GAPs, GEFs, GDIs and…now, GEMs: New kids on the heterotrimeric G protein signaling block.Cell cycle (Georgetown, Tex.) · 2017Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Trimeric G protein signaling is a fundamental mechanism of cellular communication in eukaryotes. The core of this mechanism consists of activation of G proteins by the guanine-nucleotide exchange factor (GEF) activity of G protein coupled receptors. However, the duration and amplitude of G protein-mediated signaling are controlled by a complex network of accessory proteins that appeared and diversified during evolution. Among them, nonreceptor proteins with GEF activity are the least characterized. We recently found that proteins of the ccdc88 family possess a Gα-binding and activating (GBA) motif that confers GEF activity and regulates mammalian cell behavior. A sequence similarity-based search revealed that ccdc88 genes are highly conserved across metazoa but the GBA motif is absent in most invertebrates. This prompted us to investigate whether the GBA motif is present in other nonreceptor proteins in invertebrates. An unbiased bioinformatics search in Caenorhabditis elegans identified GBAS-1 (GBA and SPK domain containing-1) as a GBA motif-containing protein with homologs only in closely related worm species. We demonstrate that GBAS-1 has GEF activity for the nematode G protein GOA-1 and that the two proteins are coexpressed in many cells of living worms. Furthermore, we show that GBAS-1 can activate mammalian Gα-subunits and provide structural insights into the evolutionarily conserved determinants of the GBA-G protein interface. These results demonstrate that the GBA motif is a functional GEF module conserved among highly divergent proteins across evolution, indicating that the GBA-Gα binding mode is strongly constrained under selective pressure to mediate receptor-independent G protein activation in metazoans.
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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.